bims-novged Biomed News
on Non-viral vectors for gene delivery
Issue of 2022–10–30
thirty-two papers selected by
the Merkel lab, Ludwig-Maximilians University
  1. Lipid Nanoparticles: A Novel Gene Delivery Technique for Clinical Application.
  2. Delivery of RNAs to Specific Organs by Lipid Nanoparticles for Gene Therapy.
  3. Recent approaches to mRNA vaccine delivery by lipid-based vectors prepared by continuous-flow microfluidic devices.
  4. Cytoplasmic delivery of siRNA using human-derived membrane penetration-enhancing peptide.
  5. Development of a Combined Lipid-Based Nanoparticle Formulation for Enhanced siRNA Delivery to Vascular Endothelial Cells.
  6. Development of lipid nanoparticles and liposomes reference materials (II): cytotoxic profiles.
  7. Targeted co-delivery of paclitaxel and anti P-gp shRNA by low molecular weight PEI decorated with L-3,4-dihydroxyphenylalanine.
  8. Design of SaCas9-HF for In Vivo Gene Therapy.
  9. Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer.
  10. Thermo-Responsive Polymer-siRNA Conjugates Enabling Artificial Control of Gene Silencing around Body Temperature.
  11. Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy.
  12. Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of AFP-Related Liver Cancer.
  13. Recent advances in gene therapy: genetic bullets to the root of the problem.
  14. mRNA-Based Approaches to Treating Liver Diseases.
  15. A Comparison of RNA Interference via Injection and Feeding in Honey Bees.
  16. In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.
  17. Multifunctional nanocarriers for delivering siRNA and miRNA in glioblastoma therapy: advances in nanobiotechnology-based cancer therapy.
  18. Back to basics: Optimization of DNA and RNA transfer in muscle cells using recent transfection reagents.
  19. Cationic Polyethyleneimine (PEI)-Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment.
  20. Are inhaled mRNA vaccines safe and effective? A review of preclinical studies.
  21. Membrane-Specific Binding of 4 nm Lipid Nanoparticles Mediated by an Entropy-Driven Interaction Mechanism.
  22. Latest Trends in Nucleic Acids' Engineering Techniques Applied to Precision Medicine.
  23. PASylation improves pharmacokinetic of liposomes and attenuates anti-PEG IgM production: An alternative to PEGylation.
  24. Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.
  25. Characterization of the Interaction of Polymeric Micelles with siRNA: A Combined Experimental and Molecular Dynamics Study.
  26. Blood-Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles.
  27. Development and characterisation of 3D collagen-gelatin based scaffolds for breast cancer research.
  28. Editorial-Current Insights on Lipid-Based Nanosystems.
  29. Microfluidic paclitaxel-loaded lipid nanoparticle formulations for chemotherapy.
  30. Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages.
  31. Controlling the two components modified on nanoparticles to construct nanomaterials.
  32. Polymeric Nanoparticles for Inhaled Vaccines.
  1. Curr Issues Mol Biol. 2022 Oct 19. 44(10): 5013-5027
    Lipid Nanoparticles: A Novel Gene Delivery Technique for Clinical Application.
    Ryuichi Mashima, Shuji Takada.
      Lipid nanoparticles (LNPs) are an emerging vehicle for gene delivery that accommodate both nucleic acid and protein. Based on the experience of therapeutic liposomes, current LNPs have been developed based on the chemistry of lipids and RNA and on the biology of human disease. LNPs have been used for the development of Onpattro, an siRNA drug for transthyretin-mediated amyloidosis, in 2018. The subsequent outbreak of COVID-19 required a vaccine for its suppression. LNP-based vaccine production received much attention for this and resulted in great success. In this review, the essential technology of LNP gene delivery has been described according to the chemistry for LNP production and biology for its clinical application.
    Keywords:  RNA modification; genome editing; lipid nanoparticle; lipids
    DOI:  https://doi.org/10.3390/cimb44100341
  2. Pharmaceutics. 2022 Oct 07. pii: 2129. [Epub ahead of print]14(10):
    Delivery of RNAs to Specific Organs by Lipid Nanoparticles for Gene Therapy.
    Kelly Godbout, Jacques P Tremblay.
      Gene therapy holds great promise in the treatment of genetic diseases. It is now possible to make DNA modifications using the CRISPR system. However, a major problem remains: the delivery of these CRISPR-derived technologies to specific organs. Lipid nanoparticles (LNPs) have emerged as a very promising delivery method. However, when delivering LNPs intravenously, most of the cargo is trapped by the liver. Alternatively, injecting them directly into organs, such as the brain, requires more invasive procedures. Therefore, developing more specific LNPs is crucial for their future clinical use. Modifying the composition of the lipids in the LNPs allows more specific deliveries of the LNPs to some organs. In this review, we have identified the most effective compositions and proportions of lipids for LNPs to target specific organs, such as the brain, lungs, muscles, heart, liver, spleen, and bones.
    Keywords:  CRISPR/Cas9 delivery; gene therapy; lipid nanoparticles; mRNA delivery; specific organ delivery
    DOI:  https://doi.org/10.3390/pharmaceutics14102129
  3. Future Med Chem. 2022 Oct 27.
    Recent approaches to mRNA vaccine delivery by lipid-based vectors prepared by continuous-flow microfluidic devices.
    Mahtab Ghasemi Toudeshkchouei, Atefeh Tavakoli, Hossein Mohammadghasemi, Anita Karimi, Jafar Ai, Mohammad Rabiee, Navid Rabiee.
      Advancements in nanotechnology have resulted in the introduction of several nonviral delivery vectors for the nontoxic, efficient delivery of encapsulated mRNA-based vaccines. Lipid- and polymer-based nanoparticles (NP) have proven to be the most potent delivery systems, providing increased delivery efficiency and protection of mRNA molecules from degradation. Here, the authors provide an overview of the recent studies carried out using lipid NPs and their functionalized forms, polymeric and lipid-polymer hybrid nanocarriers utilized mainly for the encapsulation of mRNAs for gene and immune therapeutic applications. A microfluidic system as a prevalent methodology for the preparation of NPs with continuous flow enables NP size tuning, rapid mixing and production reproducibility. Continuous-flow microfluidic devices for lipid and polymeric encapsulated RNA NP production are specifically reviewed.
    Keywords:  SARS-CoV-2 mRNA vaccine; continuous-flow microfluidic; lipid nanoparticles; lipid-polymer hybrid nanoparticles; non-viral delivery vectors
    DOI:  https://doi.org/10.4155/fmc-2022-0027
  4. J Nanobiotechnology. 2022 Oct 27. 20(1): 458
    Cytoplasmic delivery of siRNA using human-derived membrane penetration-enhancing peptide.
    Momoko Nakamura, Kei Fujiwara, Nobuhide Doi.
       BACKGROUND: Although protein-based methods using cell-penetrating peptides such as TAT have been expected to provide an alternative approach to siRNA delivery, the low efficiency of endosomal escape of siRNA/protein complexes taken up into cells by endocytosis remains a problem. Here, to overcome this problem, we adopted the membrane penetration-enhancing peptide S19 from human syncytin 1 previously identified in our laboratory.
    RESULTS: We prepared fusion proteins in which the S19 and TAT peptides were fused to the viral RNA-binding domains (RBDs) as carrier proteins, added the RBD-S19-TAT/siRNA complex to human cultured cells, and investigated the cytoplasmic delivery of the complex and the knockdown efficiency of target genes. We found that the intracellular uptake of the RBD-S19-TAT/siRNA complex was increased compared to that of the RBD-TAT/siRNA complex, and the expression level of the target mRNA was decreased. Because siRNA must dissociate from RBD and bind to Argonaute 2 (Ago2) to form the RNA-induced silencing complex (RISC) after the protein/siRNA complex is delivered into the cytoplasm, a dilemma arises: stronger binding between RBD and siRNA increases intracellular uptake but makes RISC formation more difficult. Thus, we next prepared fusion proteins in which the S19 and TAT peptides were fused with Ago2 instead of RBD and found that the efficiencies of siRNA delivery and knockdown obtained using TAT-S19-Ago2 were higher than those using TAT-Ago2. In addition, we found that the smallest RISC delivery induced faster knockdown than traditional siRNA lipofection, probably due to the decreased time required for RISC formation in the cytoplasm.
    CONCLUSION: These results indicated that S19 and TAT-fused siRNA-binding proteins, especially Ago2, should be useful for the rapid and efficient delivery of siRNA without the addition of any endosome-disrupting agent.
    Keywords:  Argonaute 2; Cell-penetrating peptide; Endosomal escape; Fusogenic peptide; Gene knockdown
    DOI:  https://doi.org/10.1186/s12951-022-01667-4
  5. Pharmaceutics. 2022 Sep 29. pii: 2086. [Epub ahead of print]14(10):
    Development of a Combined Lipid-Based Nanoparticle Formulation for Enhanced siRNA Delivery to Vascular Endothelial Cells.
    Yutong He, Dongdong Bi, Josée A Plantinga, Grietje Molema, Jeroen Bussmann, Jan A A M Kamps.
      Low transfection efficiency in endothelial cells (EC) is still a bottleneck for the majority of siRNA-based vascular delivery approaches. In this work, we developed a lipid-based nanoparticle (LNP) formulation based on a combination of a permanently charged cationic lipid-DOTAP and a conditionally ionized cationic lipid-MC3 (DOTAP/MC3) for the enhanced delivery of siRNA into EC. Compared with a single DOTAP or MC3-based benchmark LNP, we demonstrated that the DOTAP/MC3 LNP formulation shows the best transfection efficiency both in primary EC in vitro and in endothelium in zebrafish. The high transfection activity of the DOTAP/MC3 LNP formulation is achieved by a combination of improved endothelial association mediated by DOTAP and MC3-triggered efficient siRNA intracellular release in EC. Furthermore, AbVCAM-1-coupled DOTAP/MC3 LNP-mediated siRNARelA transfection showed pronounced anti-inflammatory effects in inflammatory-activated primary EC by effectively blocking the NF-κB pathway. In conclusion, the combination of permanent and ionizable cationic lipids in LNP formulation provides an effective endothelial cell delivery of siRNA.
    Keywords:  cationic lipid formulation; endothelial cell delivery; lipid-based nanoparticles; siRNA therapy; zebrafish model
    DOI:  https://doi.org/10.3390/pharmaceutics14102086
  6. Sci Rep. 2022 Oct 27. 12(1): 18071
    Development of lipid nanoparticles and liposomes reference materials (II): cytotoxic profiles.
    Krishnapriya Syama, Zygmunt J Jakubek, Sam Chen, Josh Zaifman, Yuen Yi C Tam, Shan Zou.
      Lipid based nanocarriers are one of the most effective drug delivery systems that is evident from the recent COVID-19 mRNA vaccines. The main objective of this study was to evaluate toxicity of six lipid based formulations with three surface charges-anionic, neutral or cationic, to establish certified reference materials (CRMs) for liposomes and siRNA loaded lipid nanoparticles (LNP-siRNA). Cytotoxicity was assessed by a proliferation assay in adherent and non-adherent cell lines. High concentration of three LNP-siRNAs did not affect viability of suspension cells and LNP-siRNAs were non-toxic to adherent cells at conventionally used concentration. Systematic evaluation using multiple vials and repeated test runs of three liposomes and three LNP-siRNA formulations showed no toxicity in HL60 and A549 cells up to 128 and 16 µg/mL, respectively. Extended treatment and low concentration of LNPs did not affect the viability of suspension cells and adherent cells at 96 h. Interestingly, 80% of A549 and HL60 cells in 3D conditions were viable when treated with cationic LNP-siRNA for 48 h. Taken together, anionic, cationic and neutral lipid formulations were non-toxic to cells and may be explored further in order to develop them as drug carriers.
    DOI:  https://doi.org/10.1038/s41598-022-23013-2
  7. Biotechnol Prog. 2022 Oct 28. e3310
    Targeted co-delivery of paclitaxel and anti P-gp shRNA by low molecular weight PEI decorated with L-3,4-dihydroxyphenylalanine.
    Maryam Kazemi, Elahehnaz Parhizkar, Soliman Mohammadi Samani, Omidreza Firuzi, Hossein Sadeghpour, Fatemeh Ahmadi, Ali Dehshahri.
      Co-delivery of small chemotherapeutic molecules and nucleic acid materials via targeted carriers has attracted great attention for treatment of resistant tumors and reducing adverse effects. In this study, a targeted carrier for co-delivery was prepared based on low molecular weight polyethylenimine (LMW PEI). Paclitaxel was covalently conjugated onto PEI via a succinate linker. The PEI conjugate was decorated with L-DOPA in order to target large neutral amino acid transporter-1 (LAT-1) that is over-expressed on various cancer cells. This PEI conjugate was complexed with human ABCB1 shRNA plasmid to down-regulate the expression of P-glycoprotein, as one of the major efflux pumps inducing resistance against chemotherapeutics. The formation of PEI conjugate enhanced the solubility of PTX and resulted in the condensation and protection of plasmid DNA in nano-sized polyplexes. The results of targeted delivery into the cells demonstrated that the PEI conjugate transferred the payloads to the cells over-expressing LAT-1 transporter, while the biological effects on the cells lacking the transporter was negligible. Also, shRNA-mediated down-regulation of P-gp led to the increase of toxic effects on the cells over-expressing P-gp. This study suggests a promising approach for co-delivery of small molecules and nucleic acid materials in a targeted manner for cancer therapy. This article is protected by copyright. All rights reserved.
    Keywords:  Co-delivery; Nanoparticle; P-glycoprotein; Paclitaxel; Polyethylenimine
    DOI:  https://doi.org/10.1002/btpr.3310
  8. Methods Mol Biol. 2023 ;2575 261-268
    Design of SaCas9-HF for In Vivo Gene Therapy.
    Kartikeya Tiwari, Ritesh Kumar, Prakash Saudagar.
      Genome alteration results in several diseases for which therapeutics are limited. Gene editing provides a strong and potential alternative for the treatment of rare and genetic diseases. CRISPR-Cas9-based system is now being envisaged as a potential tool for the cure of genetic diseases. The RNA-guided nuclease, SaCas9 enzyme, along with its HF versions is widely employed for in vivo gene editing because of its small size and high efficiency. The current work summarizes the widely used and improved methods for in vivo manipulation of genes. The potential of CRISPR-Cas9-based systems can be harnessed to treat genetic diseases and holds great promise for therapeutic interventions in gene therapy. The in vivo gene editing poses a caveat in the form of delivery systems, the tissue in question, and several other factors. This work describes the methods which have been optimized to offer high efficiency, delivery, and gene editing in vivo.
    Keywords:  CRISPR-Cas9; In vivo gene editing; SaCas9 HF
    DOI:  https://doi.org/10.1007/978-1-0716-2716-7_12
  9. Pharmaceutics. 2022 Oct 10. pii: 2157. [Epub ahead of print]14(10):
    Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer.
    Chunyan Liu, Wenli Zhao, Ligang Zhang, Huamin Sun, Xi Chen, Ning Deng.
      Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.
    Keywords:  OC-2; breast cancer; cRGD; cationic liposomes; shRNA
    DOI:  https://doi.org/10.3390/pharmaceutics14102157
  10. Pharm Res. 2022 Oct 28.
    Thermo-Responsive Polymer-siRNA Conjugates Enabling Artificial Control of Gene Silencing around Body Temperature.
    Yuto Honda, Sayaka Onodera, Hiroyasu Takemoto, Noor Faizah Che Harun, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Yudi Sun, Yutaka Miura, Nobuhiro Nishiyama.
       PURPOSE: Controlling small interfering RNA (siRNA) activity by external stimuli is useful to exert a selective therapeutic effect at the target site. This study aims to develop a technology to control siRNA activity in a thermo-responsive manner, which can be utilized even at temperatures close to body temperature.
    METHODS: siRNA was conjugated with a thermo-responsive copolymer that was synthesized by copolymerization of N-isopropylacrylamide (NIPAAm) and hydrophilic N,N-dimethylacrylamide (DMAA) to permit thermally controlled interaction between siRNA and an intracellular gene silencing-related protein by utilizing the coil-to-globule phase transition of the copolymer. The composition of the copolymer was fine-tuned to obtain lower critical solution temperature (LCST) around body temperature, and the phase transition behavior was evaluated. The cellular uptake and gene silencing efficiency of the copolymer-siRNA conjugates were then investigated in cultured cells.
    RESULTS: The siRNA conjugated with the copolymer with LCST of 38.0°C exhibited ~ 11.5 nm of the hydrodynamic diameter at 37°C and ~ 9.8 nm of the diameter at 41°C, indicating the coil-globule transition above the LCST. In line with this LCST behavior, its cellular uptake and gene silencing efficiency were enhanced when the temperature was increased from 37°C to 41°C.
    CONCLUSION: By fine-tuning the LCST behavior of the copolymer that was conjugated with siRNA, siRNA activity could be controlled in a thermo-responsive manner around the body temperature. This technique may offer a promising approach to induce therapeutic effects of siRNA selectively in the target site even in the in vivo conditions.
    Keywords:  nucleic acid delivery; polymer-siRNA conjugates; thermo-responsiveness
    DOI:  https://doi.org/10.1007/s11095-022-03414-8
  11. Bioengineering (Basel). 2022 Oct 19. pii: 576. [Epub ahead of print]9(10):
    Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy.
    Shuaiying Wu, Chao Liu, Shuang Bai, Zhixiang Lu, Gang Liu.
      RNA-based therapy is a promising and innovative strategy for cancer treatment. However, poor stability, immunogenicity, low cellular uptake rate, and difficulty in endosomal escape are considered the major obstacles in the cancer therapy process, severely limiting the development of clinical translation and application. For efficient and safe transport of RNA into cancer cells, it usually needs to be packaged in appropriate carriers so that it can be taken up by the target cells and then be released to the specific location to perform its function. In this review, we will focus on up-to-date insights of the RNA-based delivery carrier and comprehensively describe its application in cancer therapy. We briefly discuss delivery obstacles in RNA-mediated cancer therapy and summarize the advantages and disadvantages of different carriers (cationic polymers, inorganic nanoparticles, lipids, etc.). In addition, we further summarize and discuss the current RNA therapeutic strategies approved for clinical use. A comprehensive overview of various carriers and emerging delivery strategies for RNA delivery, as well as the current status of clinical applications and practice of RNA medicines are classified and integrated to inspire fresh ideas and breakthroughs.
    Keywords:  RNA delivery; cancer therapy; clinical practice; delivery carrier
    DOI:  https://doi.org/10.3390/bioengineering9100576
  12. Int J Mol Sci. 2022 Oct 21. pii: 12666. [Epub ahead of print]23(20):
    Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of AFP-Related Liver Cancer.
    Kittiporn Punuch, Chamaiphorn Wongwan, Saranrat Jantana, Chayapol Somboonyosdech, Kamonlatth Rodponthukwaji, Natsuda Kunwong, Kytai T Nguyen, Vorapan Sirivatanauksorn, Yongyut Sirivatanauksorn, Chatchawan Srisawat, Primana Punnakitikashem.
      Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (AFP-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The AFP siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of AFP-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. AFP-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that AFP-siRNA incorporated with NPs could significantly silence AFP-mRNA expression compared to unloaded NPs. Interestingly, the expression level of AFP-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.
    Keywords:  alpha-fetoprotein (AFP); angiogenesis inhibitor; hepatocellular carcinoma (HCC); nanoparticle (NP); polylactic-co-glycolic acid (PLGA); small interfering RNA (siRNA)
    DOI:  https://doi.org/10.3390/ijms232012666
  13. Clin Exp Med. 2022 Oct 25.
    Recent advances in gene therapy: genetic bullets to the root of the problem.
    Mohsen Danaeifar.
      Genetics and molecular genetic techniques have changed many perspectives and paradigms in medicine. Using genetic methods, many diseases have been cured or alleviated. Gene therapy, in its simplest definition, is application of genetic materials and related techniques to treat various human diseases. Evaluation of the trends in the field of medicine and therapeutics clarifies that gene therapy has attracted a lot of attention due to its powerful potential to treat a number of diseases. There are various genetic materials that can be used in gene therapy such as DNA, single- and double-stranded RNA, siRNA and shRNA. The main gene editing techniques used for in vitro and in vivo gene modification are ZNF, TALEN and CRISPR-Cas9. The latter has increased hopes for more precise and efficient gene targeting as it requires two separate recognition sites which makes it more specific and can also cause rapid and sufficient cleavage within the target sequence. There must be carriers for delivering genes to the target tissue. The most commonly used carriers for this purpose are viral vectors such as adenoviruses, adeno-associated viruses and lentiviruses. Non-viral vectors consist of bacterial vectors, liposomes, dendrimers and nanoparticles.
    Keywords:  Gene editing; Gene therapy; Genetics; Vector; Virus
    DOI:  https://doi.org/10.1007/s10238-022-00925-x
  14. Cells. 2022 Oct 21. pii: 3328. [Epub ahead of print]11(20):
    mRNA-Based Approaches to Treating Liver Diseases.
    Maximiliano L Cacicedo, María José Limeres, Stephan Gehring.
      Diseases that affect the liver account for approximately 2 million deaths worldwide each year. The increasing prevalence of these diseases and the limited efficacy of current treatments are expected to stimulate substantial growth in the global market for therapeutics that target the liver. Currently, liver transplantation is the only curative option available for many liver diseases. Gene therapy represents a valuable approach to treatment. The liver plays a central role in a myriad of essential metabolic functions, making it an attractive organ for gene therapy; hepatocytes comprise the most relevant target. To date, viral vectors constitute the preferred approach to targeting hepatocytes with genes of therapeutic interest. Alternatively, mRNA-based therapy offers a number of comparative advantages. Clinical and preclinical studies undertaken to treat inherited metabolic diseases affecting the liver, cirrhosis and fibrosis, hepatocellular carcinoma, hepatitis B, and cytomegalovirus using lipid nanoparticle-encapsulated mRNAs that encode the therapeutic or antigenic protein of interest are discussed.
    Keywords:  cirrhosis; hepatocellular carcinoma; inherited metabolic diseases; lipid nanoparticles; therapeutic mRNA constructs
    DOI:  https://doi.org/10.3390/cells11203328
  15. Insects. 2022 Oct 13. pii: 928. [Epub ahead of print]13(10):
    A Comparison of RNA Interference via Injection and Feeding in Honey Bees.
    Yong Zhang, Zhen Li, Zi-Long Wang, Li-Zhen Zhang, Zhi-Jiang Zeng.
      RNA interference (RNAi) has been used successfully to reduce target gene expression and induce specific phenotypes in several species. It has proved useful as a tool to investigate gene function and has the potential to manage pest populations and reduce disease pathogens. However, it is not known whether different administration methods are equally effective at interfering with genes in bees. Therefore, we compared the effects of feeding and injection of small interfering RNA (siRNA) on the messenger RNA (mRNA) levels of alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1), 4-coumarate-CoA ligase (4CL), and heat shock protein 70 (HSP70). Both feeding and injection of siRNA successfully knocked down the gene but feeding required more siRNA than the injection. Our results suggest that both feeding and injection of siRNA effectively interfere with brain genes in bees. The appropriateness of each method would depend on the situation.
    Keywords:  RNAi; brain; honey bee; siRNA
    DOI:  https://doi.org/10.3390/insects13100928
  16. Int J Pharm. 2022 Oct 22. pii: S0378-5173(22)00890-0. [Epub ahead of print] 122335
    In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.
    Phuoc Vinh Nguyen, Katel Hervé-Aubert, Laurie Lajoie, Yoann Misericordia, Igor Chourpa, Stéphanie David, Emilie Allard-Vannier.
      Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents. In this study, anti-Bcl-xL siRNA were formulated within an EGFR-targeted nanomedicine with scFv ligands (NM-scFv) and its activity was tested in the non-small cell lung cancer (NSCLC) cell line H460. The obtained NMs-scFv anti-Bcl-xL were suitable for intravenous injection with sizes around 100 nm, a high monodispersity level and good siRNA complexation capacity. The nanocomplex's functionalization with anti-EGFR scFv ligands was shown to allow an active gene delivery into H460 cells and led to approximately 63% of gene silencing at both mRNA and protein levels. The NM-scFv anti-Bcl-xL improved the apoptotic activity of cisplatin and reduced the cisplatin IC50 value in H460 cells by a factor of around three from 0.68 ± 0.12 µM to 2.21 ± 0.18 µM (p<0.01), respectively, in comparison to that of NM-scFv formulated with control siRNA (p>0.05).
    Keywords:  BcL-xL; EGFR-targeted nanomedicine; NSCLC; cisplatin; gene delivery; scFv
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122335
  17. 3 Biotech. 2022 Nov;12(11): 301
    Multifunctional nanocarriers for delivering siRNA and miRNA in glioblastoma therapy: advances in nanobiotechnology-based cancer therapy.
    Karishma Shetty, Soma Yasaswi, Shilpee Dutt, Khushwant S Yadav.
      Glioblastoma multiforme (GBM) is one of the most lethal cancer due to poor diagnosis and rapid resistance developed towards the drug. Genes associated to cancer-related overexpression of proteins, enzymes, and receptors can be suppressed using an RNA silencing technique. This assists in obtaining tumour targetability, resulting in less harm caused to the surrounding healthy cells. RNA interference (RNAi) has scientific basis for providing potential therapeutic applications in improving GBM treatment. However, the therapeutic application of RNAi is challenging due to its poor permeability across blood-brain barrier (BBB). Nanobiotechnology has evolved the use of nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, dendrimers, quantum dots and other nanostructures in encasing the RNAi entities like siRNA and miRNA. The review highlights the role of these carriers in encasing siRNA and miRNA and promising therapy in delivering them to the glioma cells.
    Keywords:  Glioblastoma; Multifunctional nanocarriers; miRNA; siRNA
    DOI:  https://doi.org/10.1007/s13205-022-03365-2
  18. Exp Cell Res. 2022 Oct 20. pii: S0014-4827(22)00385-8. [Epub ahead of print] 113392
    Back to basics: Optimization of DNA and RNA transfer in muscle cells using recent transfection reagents.
    Ilaria Cocchiararo, Mélanie Cornut, Hadrien Soldati, Alessandro Bonavoglia, Perrine Castets.
      C2C12 cells are widely used in the muscle field, as they differentiate easily into myotubes and show limited constraints to culture as compared to primary myoblasts. Both C2C12 and primary myoblasts are hard to transfect, which affects downstream experiments. More than 95% of the reports published since 2015 with C2C12 cells have used one gold standard transfectant (i.e., Lipofectamine®), although several studies have suggested less than 30% efficiency of this reagent. In parallel, the capacity of other commercial reagents to transfect muscle cells remains largely unknown. Here, we compared transfection efficiency of five commercial reagents (Lipofectamine® 3000, Viafect™, Fugene® HD, C2C12 Cell Avalanche®, and JetOPTIMUS®) in C2C12 cells. By optimizing DNA:transfectant ratios and cell density, all reagents reached more than 60% transfection efficiency with limited effects on cell growth and viability. GFP-positive myotubes were efficiently generated in cultures transfected with Lipofectamine® 3000, Fugene® HD, C2C12 Cell Avalanche®, and JetOPTIMUS®. Notably, in conditions optimized for DNA transfer in C2C12 cells, these reagents showed low efficiency to transfer siRNA and higher toxicity for primary muscle cells. In conclusion, we reported yet uncharacterized transfection reagents that can serve as a suitable low-cost alternative to the current gold standard in C2C12 cells.
    Keywords:  C2C12; Differentiation; Myoblast; Transfection; Viability; siRNA
    DOI:  https://doi.org/10.1016/j.yexcr.2022.113392
  19. Pharmaceutics. 2022 Oct 19. pii: 2234. [Epub ahead of print]14(10):
    Cationic Polyethyleneimine (PEI)-Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment.
    Vladimir Mulens-Arias, Alba Nicolás-Boluda, Florent Carn, Florence Gazeau.
      Nanomedicines based on inorganic nanoparticles have grown in the last decades due to the nanosystems' versatility in the coating, tuneability, and physical and chemical properties. Nonetheless, concerns have been raised regarding the immunotropic profile of nanoparticles and how metallic nanoparticles affect the immune system. Cationic polymer nanoparticles are widely used for cell transfection and proved to exert an adjuvant immunomodulatory effect that improves the efficiency of conventional vaccines against infection or cancer. Likewise, gold nanoparticles (AuNPs) also exhibit diverse effects on immune response depending on size or coatings. Photothermal or photodynamic therapy, radiosensitization, and drug or gene delivery systems take advantage of the unique properties of AuNPs to deeply modify the tumoral ecosystem. However, the collective effects that AuNPs combined with cationic polymers might exert on their own in the tumor immunological microenvironment remain elusive. The purpose of this study was to analyze the triple-negative breast tumor immunological microenvironment upon intratumoral injection of polyethyleneimine (PEI)-AuNP nanocomposites (named AuPEI) and elucidate how it might affect future immunotherapeutic approaches based on this nanosystem. AuPEI nanocomposites were synthesized through a one-pot synthesis method with PEI as both a reducing and capping agent, resulting in fractal assemblies of about 10 nm AuNPs. AuPEI induced an inflammatory profile in vitro in the mouse macrophage-like cells RAW264.7 as determined by the secretion of TNF-α and CCL5 while the immunosuppressor IL-10 was not increased. However, in vivo in the mouse breast MET-1 tumor model, AuPEI nanocomposites shifted the immunological tumor microenvironment toward an M2 phenotype with an immunosuppressive profile as determined by the infiltration of PD-1-positive lymphocytes. This dichotomy in AuPEI nanocomposites in vitro and in vivo might be attributed to the highly complex tumor microenvironment and highlights the importance of testing the immunogenicity of nanomaterials in vitro and more importantly in vivo in relevant immunocompetent mouse tumor models to better elucidate any adverse or unexpected effect.
    Keywords:  cationic nanostructure; gold; immune cells; nanoparticles; polyethyleneimine; tumor microenvironment
    DOI:  https://doi.org/10.3390/pharmaceutics14102234
  20. Expert Opin Drug Deliv. 2022 Oct 26. 1-15
    Are inhaled mRNA vaccines safe and effective? A review of preclinical studies.
    Evalyne M Jansen, Henderik W Frijlink, Wouter Lj Hinrichs, Mitchel Jr Ruigrok.
       INTRODUCTION: Injected mRNA vaccines have been proven effective and safe in the SARS-CoV-2 pandemic. Using the machinery of the cell, mRNA vaccines translate into an antigen, which triggers an adaptive immune response. The effectiveness of intramuscular administered mRNA vaccines wanes in the months post-vaccination, which makes frequent booster administrations necessary. To make booster administration easier and increase efficacy, pulmonary administration could be investigated. The aim of this literature study was therefore to review the published preclinical (animal) studies on the safety and efficacy of pulmonary administered mRNA vaccines.
    AREAS COVERED: We first provide background information on mRNA vaccines and immunological mechanisms of vaccination. Thereafter, we provide an evaluation of published animal studies, in which mRNA vaccines (or mRNA containing nanoparticles) were delivered into the lungs. We covered the following areas: biodistribution, cellular uptake, immune response, protection, and safety. All relevant papers were found using PubMed/MEDLINE database.
    EXPERT OPINION: In our opinion, head-to-head comparison studies examining the safety and efficacy of intramuscular injected and pulmonary administered liquid mRNA vaccines should be performed first. When pulmonary delivered mRNA vaccines are shown to be effective and safe, inhalable dry powder formulations should be engineered. Finally, the tolerability of patients with respiratory diseases should be considered.
    Keywords:  Lung delivery; SARS-CoV-2; mRNA nanoparticle; mRNA vaccine; mRNA-LNP; mucosal immunity; pulmonary administration
    DOI:  https://doi.org/10.1080/17425247.2022.2131767
  21. ACS Nano. 2022 Oct 24.
    Membrane-Specific Binding of 4 nm Lipid Nanoparticles Mediated by an Entropy-Driven Interaction Mechanism.
    Luping Ou, Haibo Chen, Bing Yuan, Kai Yang.
      Lipid nanoparticles (LNPs) are a leading biomimetic drug delivery platform due to their distinctive advantages and highly tunable formulations. A mechanistic understanding of the interaction between LNPs and cell membranes is essential for developing the cell-targeted carriers for precision medicine. Here the interactions between sub 10 nm cationic LNPs (cLNPs; e.g., 4 nm in size) and varying model cell membranes are systematically investigated using molecular dynamics simulations. We find that the membrane-binding behavior of cLNPs is governed by a two-step mechanism that is initiated by direct contact followed by a more crucial lipid exchange (dissociation of cLNP's coating lipids and subsequent flip and intercalation into the membrane). Importantly, our simulations demonstrate that the membrane binding of cLNPs is an entropy-driven process, which thus enables cLNPs to differentiate between membranes having different lipid compositions (e.g., the outer and inner membranes of bacteria vs the red blood cell membranes). Accordingly, the possible strategies to drive the membrane-targeting behaviors of cLNPs, which mainly depend on the entropy change in the complicated entropy-enthalpy competition of the cLNP-membrane interaction process, are investigated. Our work unveils the molecular mechanism underlying the membrane selectivity of cLNPs and provides useful hints to develop cLNPs as membrane-targeting agents for precision medicine.
    Keywords:  entropy-driven process; lipid nanoparticles; membrane-specific binding; molecular dynamics simulations; targeted delivery
    DOI:  https://doi.org/10.1021/acsnano.2c04774
  22. Methods Mol Biol. 2023 ;2575 25-38
    Latest Trends in Nucleic Acids' Engineering Techniques Applied to Precision Medicine.
    Glaucia C Pereira.
      Nucleic acids are paving the way for advanced therapeutics. Unveiling the genome enabled a better understanding of unique genotype-phenotype profiling. Methods for engineering and analysis of nucleic acids, from polymerase chain reaction to Cre-Lox recombination, are contributing greatly to biomarkers' discovery, mapping of cellular signaling cascades, and smart design of therapeutics in precision medicine. Investigating the different subtypes of DNA and RNA via sequencing and profiling is empowering the scientific community with valuable information, to be used in advanced therapeutics, tracking epigenetics linked to disease. Recent results from the application of nucleic acids in novel therapeutics and precision medicine are very encouraging, demonstrating great potential to treat cancer, viral infections via inoculation (e.g., SAR-COV-2 mRNA vaccines), along with metabolic and genetic disorders. Limitations posed by challenges in delivery mode are being addressed to enable efficient guided-gene-programmed precision therapies. With the focus on genetic engineering and novel therapeutics, more precisely, in precision medicine, this chapter discusses the advance enabled by knowledge derived from these innovative branches of biotechnology.
    Keywords:  CRISPR-Cas9; Cancer research; Cre-Lox recombination; DNA; Genetic engineering; Infectology; Metabolic diseases; Nanotechnology; Nucleic acids; Precision medicine; RNA
    DOI:  https://doi.org/10.1007/978-1-0716-2716-7_2
  23. Nanomedicine. 2022 Oct 21. pii: S1549-9634(22)00108-3. [Epub ahead of print] 102622
    PASylation improves pharmacokinetic of liposomes and attenuates anti-PEG IgM production: An alternative to PEGylation.
    Qianyu Zhang, Sai Li, Wen Wu, Xuefeng Xia, Jinqiang Zhang.
      PASylation, which was recently reported as the conjugation of pharmacologically active compounds with polypeptide sequences mainly made of proline, alanine and serine, has been proposed as an alternative to PEGylation. In this study, we designed PAS-modified liposomes (PASylated liposomes) and studied the effect of the incorporation of PAS-lipid on the stability and pharmacokinetic properties of liposomes, and compared them both in vitro and in vivo to PEGylated liposomes. Results showed that PASylated liposomes modified with single-chained PAS-lipid C16-(PA3)7 (SC-PAS-Lip) showed comparable storage and serum stability to PEGylated liposomes (PEG-Lip), and a significantly decreased macrophage uptake compared with unmodified liposomes. SC-PAS-Lip displayed long circulating pharmacokinetic profile which was not impacted by the repeated administration of liposomes, and they were less likely to induce the production of anti-PEG IgM compared with PEGylated liposomes, presenting PASylation as an alternative liposome modification strategy to PEGylation.
    Keywords:  Anti-PEG IgM; Liposomes; PASylation; PEGylation
    DOI:  https://doi.org/10.1016/j.nano.2022.102622
  24. Colloids Surf B Biointerfaces. 2022 Oct 10. pii: S0927-7765(22)00595-1. [Epub ahead of print]220 112911
    Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.
    Nazanin Amiryaghoubi, Elaheh Dalir Abdolahinia, Ailar Nakhlband, Shaghayegh Aslzad, Marziyeh Fathi, Jaleh Barar, Yadollah Omidi.
      Chitosan (CS)-based pH-sensitive nanocomposites were fabricated for the targeted delivery of doxorubicin (DOX) to osteosarcoma cells. To prepare the nanocomposite, CS was functionalized with succinic anhydride (SA) (CS-SA). CS-folic acid (FA) conjugates were produced by the conjugation of CS with FA via an amide bond. Next, Fe3O4 magnetic nanoparticles (MNPs) ferrofluid was fabricated, and nanocomposite was produced using MNPs and synthesized CS-SA/CS-FA and CS-SA via an inclusion formation between -COOH groups of CS-SA and hydroxyl groups of Fe3O4. Finally, DOX molecules were loaded onto the nanocomposites. The nanocomposites were characterized through FT-IR, DLS, XRD, VSM, TEM, and UV-Vis spectroscopy analyses. DOX release profile at various pHs indicated an enhanced release of DOX in acidic conditions. The cytotoxicity assay demonstrated that the nanocarriers alone were cytocompatible on cells examined. The MG-63 cells, which partly express the folate receptors (FRs), particularly FR-α, showed meaningfully higher cellular uptake of the DOX-loaded CS-FA/CS-SA@MNPs than the FR-negative lung cancer A549 cells. The DOX-loaded CS-FA/CS-SA-MNPs could induce significant cytotoxicity in the MG-63 cells but not in A549 cells. Based on these findings, the DOX-loaded CS-FA/ CS-SA-MNPs might be considered a smart pH-sensitive nanosystem for the targeted delivery of anticancer agents to osteosarcoma cancer cells.
    Keywords:  Cancer; Chitosan; Doxorubicin; Folate receptor; Magnetic nanoparticles; Osteosarcoma; Targeted drug delivery
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112911
  25. Polymers (Basel). 2022 Oct 19. pii: 4409. [Epub ahead of print]14(20):
    Characterization of the Interaction of Polymeric Micelles with siRNA: A Combined Experimental and Molecular Dynamics Study.
    Franck Marquet, Filip Stojceski, Gianvito Grasso, Viorica Patrulea, Andrea Danani, Gerrit Borchard.
      The simulation of large molecular systems remains a daunting challenge, which justifies the exploration of novel methodologies to keep computers as an ideal companion tool for everyday laboratory work. Whole micelles, bigger than 20 nm in size, formed by the self-assembly of hundreds of copolymers containing more than 50 repeating units, have until now rarely been simulated, due to a lack of computational power. Therefore, a flexible amphiphilic triblock copolymer (mPEG45-α-PLL10-PLA25) containing a total of 80 repeating units, has been emulated and synthesized to embody compactified nanoconstructs of over 900 assembled copolymers, sized between 80 and 100 nm, for siRNA complexing purposes. In this study, the tailored triblock copolymers containing a controlled number of amino groups, were used as a support model to address the binding behavior of STAT3-siRNA, in the formation of micelleplexes. Since increasingly complex drug delivery systems require an ever more optimized physicochemical characterization, a converging description has been implemented by a combination of experimentation and computational simulations. The computational data were advantageous in allowing for the assumption of an optimal N/P ratio favoring both conformational rigidifications of STAT3-siRNA with low competitive phenomena at the binding sites of the micellar carriers. These calculations were consistent with the experimental data showing that an N/P ratio of 1.5 resulted in a sufficient amount of complexed STAT3-siRNA with an electrical potential at the slipping plane of the nanopharmaceuticals, close to the charge neutralization.
    Keywords:  binding affinity; capillary zone electrophoresis; complexation efficiency; isothermal titration calorimetry; molecular dynamics; polymeric micelles
    DOI:  https://doi.org/10.3390/polym14204409
  26. Pharmaceutics. 2022 Oct 19. pii: 2237. [Epub ahead of print]14(10):
    Blood-Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles.
    Maj Schneider Thomsen, Kasper Bendix Johnsen, Krzysztof Kucharz, Martin Lauritzen, Torben Moos.
      The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for the delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.
    Keywords:  antibody; blood–brain barrier; endosomal; liposome; nanoparticle; targeting; transferrin
    DOI:  https://doi.org/10.3390/pharmaceutics14102237
  27. Biomater Adv. 2022 Oct 17. pii: S2772-9508(22)00434-4. [Epub ahead of print]142 213157
    Development and characterisation of 3D collagen-gelatin based scaffolds for breast cancer research.
    John Redmond, Helen O McCarthy, Paul Buchanan, Tanya J Levingstone, Nicholas J Dunne.
      While 2D culture presents a useful tool for cancer research, it fails to replicate the tumor microenvironment as it lacks proper three-dimensional cell-cell/cell-matrix interactions, often resulting in exaggerated responses to therapeutic agents. 3D models that aim to overcome the issues associated with 2D culture research offer a new frontier for cancer research with cell growth, morphology and genetic properties that more closely match in vivo cancers. Herein, we aim to develop a collagen-based scaffold that supports the attachment and proliferation of breast cancer (BC) cells as a 3D culture model. Scaffolds were produced on a repeatable basis using a freeze-drying procedure. The constructs were highly porous (>99%) with homogenous pore sizes (150-300 μm) and an interconnected structure. The application of 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) crosslinking resulted in scaffolds with elastic moduli in the range of 1-2 kPa, mimicking cancerous breast tissue stiffness. Furthermore, the incorporation of gelatin into the scaffolds enabled the porosity, pore size and mechanical properties to be tailored, resulting in scaffolds with stiffness values that accurately replicate the stiffness of human BC extracellular matrix (ECM) (1.3-1.7 kPa). Scaffolds displayed high in vitro stability with 90% of mass remaining after 14 days of culture. The scaffolds were shown to be highly biocompatible, and capable of supporting the attachment, infiltration and proliferation of MCF7 breast cancer (BC) cells over +14 days. These results confirm the suitability of these scaffolds as culture models for BC cells. These collagen-based scaffolds offer significant potential for the exploration of aspects of BC, such as gene expression profiles and patterns, and for the assessment of the efficacy of therapeutic agents in treating BC.
    Keywords:  3D culture; Biofabrication; Breast Cancer; Collagen; Gelatin
    DOI:  https://doi.org/10.1016/j.bioadv.2022.213157
  28. Pharmaceuticals (Basel). 2022 Oct 14. pii: 1267. [Epub ahead of print]15(10):
    Editorial-Current Insights on Lipid-Based Nanosystems.
    Ana Catarina Silva, João Nuno Moreira, José Manuel Sousa Lobo.
      Lipid-based nanosystems, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), cationic lipid nanoparticles, nanoemulsions and liposomes, have been extensively studied to improve drug delivery through different administration routes [...].
    DOI:  https://doi.org/10.3390/ph15101267
  29. Int J Pharm. 2022 Oct 19. pii: S0378-5173(22)00875-4. [Epub ahead of print]628 122320
    Microfluidic paclitaxel-loaded lipid nanoparticle formulations for chemotherapy.
    Eman Jaradat, Edward Weaver, Adam Meziane, Dimitrios A Lamprou.
      Nanoparticle technology has promising effects on multiple therapeutic purposes, particularly in controlling drug delivery as Drug Delivery System. The unique properties of nanoparticles significantly enhance drug delivery, efficiency, and toxicity. For cancer therapy, controlling chemotherapy delivery can increase the drug concentration in the desired locations, improve drug efficacy, and limit drug toxicity. Liposomes are used in this project to encapsulate paclitaxel due to their ability to carry hydrophobic molecules, low toxicity, and prolonged half-life. Among the multiple liposome preparation methods, microfluidic technology was used to produce liposomes. Microfluidics excels in other conventional methods by offering a high-level control of the process's parameters, which help control particle size, size distribution, and physiochemical properties. This project aims to produce paclitaxel-loaded liposomes with a diameter below 200 nm with low polydispersity index, high homogeneity, and good stability. Different lipid types (DMPC, DPPC, DSPC, and DOPC) were used with different ratios to investigate their impact on empty liposome formulation. Alongside changing the different microfluidic parameters including the total flow ratio and flow rate ratio to study their effects on liposomes' physiochemical properties. The obtained formulations were tested to analyse different physiochemical properties (DLS, FTIR) and stability studies. DMPC and DPPC are determined to study their encapsulation efficiency and in vitro drug release of paclitaxel at total flow rate 1 ml min-1 and 1:4 flow rate ratio. The paclitaxel-loaded liposomes are subjected to the same physiochemical characteristics and stability study. Promising encapsulation efficiency was reported from both DPPC and DMPC, and sustained drug release was observed.
    Keywords:  Cancer; Chemotherapy; Emerging technologies; Liposomes; Microfluidics; Nanomedicine; Nanoparticles; Paclitaxel
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122320
  30. Pharmaceutics. 2022 Oct 05. pii: 2118. [Epub ahead of print]14(10):
    Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages.
    Shwe Phyu Hlaing, Jiafu Cao, Juho Lee, Jihyun Kim, Aruzhan Saparbayeva, Dongmin Kwak, Hyunwoo Kim, Seonghwan Hwang, Hwayoung Yun, Hyung Ryong Moon, Yunjin Jung, Jin-Wook Yoo.
      Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis.
    Keywords:  hyaluronic acid; inflamed tissue targeting; macrophage targeting; nanoparticle; ulcerative colitis therapy
    DOI:  https://doi.org/10.3390/pharmaceutics14102118
  31. Soft Matter. 2022 Oct 26.
    Controlling the two components modified on nanoparticles to construct nanomaterials.
    Yixin Zhang, Hao Tang, Rong Wang.
      Nanoparticle self-assembly technology has made great progress in the past 30 years. Many kinds of self-assembly strategies of modifiable nanoparticles have been developed and used to construct nano-aggregates by designing the shape, size and type of nanoparticles and controlling the components modified on nanoparticles. These strategies are widely used in many fields, such as medical diagnosis, biological detection, drug delivery, materials synthesis and sensors. The modified components can be DNA chains, polymer chains, proteins, and even organic molecules based on different molecular conformations and chemical properties. In recent years, the self-assembly of two-component modified nanoparticles has gradually attracted more attention. Nanoparticles modified with two components of different DNA strands can self-assemble to produce a variety of nano arrangement structures, such as BCC, FCC and other cubic crystals, which can be used in crystal materials. Two-component modification of hydrophilic and hydrophobic polymers can produce vesicular aggregates, which can be used for drug delivery. In this review, we summarize the latest experimental progress and theoretical simulation of self-assembly of two-component modified nanoparticles including different DNA chains, different polymer chains, DNA and polymer chains, proteins and polymer chains, and different organic molecules. Their self-assembly characteristics and application prospects were discussed. Compared with single-component modified nanoparticles, two-component nanoparticles have different tethered molecules or molecular chains, which can be multifunctional by regulating different modified components and types of nanoparticles and ultimately expand the scope of applications.
    DOI:  https://doi.org/10.1039/d2sm00877g
  32. Polymers (Basel). 2022 Oct 21. pii: 4450. [Epub ahead of print]14(20):
    Polymeric Nanoparticles for Inhaled Vaccines.
    Nusaiba K Al-Nemrawi, Ruba S Darweesh, Lubna A Al-Shriem, Farah S Al-Qawasmi, Sereen O Emran, Areej S Khafajah, Muna A Abu-Dalo.
      Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose.
    Keywords:  immunization; inhaled vaccine; nanoparticles; polymeric; vaccine
    DOI:  https://doi.org/10.3390/polym14204450
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:25.