bims-drudre 2022-10-09 papers

bims-drudre

Biomed News

on Targeted drug delivery and programmed release mechanisms

Issue of 2022–10–09
eightteen papers selected by
Ceren Kimna, Technical University of Munich

Oral Supramolecular Adsorbent for Preventing Chemo-Induced Gastrointestinal Mucositis & Microbial Dysbiosis and for Enhancing Chemoimmunotherapy.
Autonomous Untethered Microinjectors for Gastrointestinal Delivery of Insulin.
Strong and Tough Supramolecular Microneedle Patches with Ultrafast Dissolution and Rapid-onset Capabilities.
Heparin-Peptide Nanogranules for Thrombosis-Actuated Anticoagulation.
An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.
Light-programmable Nanocomposite Hydrogel for State-switchable Wound Healing Promotion and Bacterial Infection Elimination.
Bioinspired and Inflammation-modulatory Glycopeptide Hydrogels for Radiation-induced Chronic Skin Injury Repair.
Self-Propelled Nanomotors with Alloyed Engine for Emergency Rescue of Traumatic Brain Injury.
Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.
R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer.
Targeting to Tumor-Harbored Bacteria for Precision Tumor Therapy.
3D-printed microrobots from design to translation.
Acellularized Uvea Hydrogel As Novel Injectable Platform for Cell-based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System.
Multifunctional 4D-printed Sperm-hybrid Microcarriers for Assisted Reproduction.
Size-Controllable and Self-Assembled DNA Nanosphere for Amplified MicroRNA Imaging through ATP-Fueled Cyclic Dissociation.
Self-powered, Implantable, and Wirelessly-Controlled NO Generation System for Intracranial Neuroglioma Therapy.
Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer.
Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins.

Adv Mater. 2022 Oct 03. e2205299

Oral Supramolecular Adsorbent for Preventing Chemo-Induced Gastrointestinal Mucositis & Microbial Dysbiosis and for Enhancing Chemoimmunotherapy.

Meng Tian, Dongyue Fan, Zhen Liu, Xin Mu, Qianqian Tao, Chunyang Yu, Shiyi Zhang.

  The addition of immune checkpoint blockade (ICB) to cytotoxic chemotherapy has emerged as the first-line treatment for multiple cancers. Paradoxically, cytotoxic chemotherapy may limit the therapeutic potential of ICB by significantly impairing the largest immune organ, the gastrointestinal (GI) tract, and driving gut microbial dysbiosis. Here, we report an orally administered polymeric adsorbent containing a supramolecular motif (named SPORA-SN9) that can selectively remove chemotherapeutics from the GI tract, thereby preventing chemotherapy-induced GI mucositis and microbial dysbiosis and providing better chemoimmunotherapy synergy. By theoretical design and experimental screening of the molecular recognition motifs, SPORA-SN9 exhibits superior complexation capacity for doxorubicin and irinotecan and high selectivity over a range of commonly used combinational medications. In mouse models of chemotherapy-induced GI mucositis, SPORA-SN9 protected the integrity of the GI tissues and the homeostasis of the gut microbiota. Finally, the addition of SPORA-SN9 enhanced the efficacy of chemoimmunotherapy in tumor-bearing mice. SPORA-SN9 offers a translational approach for supramolecular chemistry to modulate complex biosystems by selectively removing target substrates from the GI tract. This article is protected by copyright. All rights reserved.

Keywords:  chemotherapy; gastrointestinal mucositis; immune checkpoint blockade; microbial dysbiosis; supramolecular adsorbents

DOI:  https://doi.org/10.1002/adma.202205299
ACS Nano. 2022 Oct 06.

Autonomous Untethered Microinjectors for Gastrointestinal Delivery of Insulin.

Arijit Ghosh, Wangqu Liu, Ling Li, Gayatri J Pahapale, Si Young Choi, Liyi Xu, Qi Huang, Ruili Zhang, Zijian Zhong, Florin M Selaru, David H Gracias.

  The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging as these drugs display low stability as well as poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that are deployed in the GI tract, then efficiently penetrate the GI mucosa to deliver a macromolecular drug, insulin, to the systemic circulation. We performed in vitro studies to characterize insulin release and assess the penetration capability of microinjectors and we measured the in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin transmucosally to the systemic circulation at levels similar to those with intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these microinjectors will significantly advance drug delivery across the GI tract mucosa to the systemic circulation in a safe manner.

Keywords:  drug delivery; oral insulin; robotics; self-folding; shape change

DOI:  https://doi.org/10.1021/acsnano.2c05098
Adv Mater. 2022 Oct 03. e2207832

Strong and Tough Supramolecular Microneedle Patches with Ultrafast Dissolution and Rapid-onset Capabilities.

Hua Wang, Yangxue Fu, Jinzhu Mao, Hao Jiang, Shuo Du, Pei Liu, Juan Tao, Lianbin Zhang, Jintao Zhu.

  Dissolving microneedle (DMN) patches are emerging as a minimally-invasive and efficient transdermal drug delivery platform. Generally, noncrystalline, water-soluble, and high-molecular-weight polymers are employed in DMN because their sufficient intermolecular interactions can endow DMN with necessary mechanical strength and toughness. However, high viscosity and heavy chain entanglement of polymer solutions greatly hinder processing and dissolution of polymeric DMNs. Here, we describe a strong and tough supramolecular DMN made of highly water-soluble cyclodextrin (CD) derivatives. Due to the synergy of multiple supramolecular interactions, CD DMN patch exhibits robust mechanical strength outperforming the state-of-the-art polymeric DMNs. CD DMN displays ultrafast dissolution (< 30 s) in skin models by virtue of the dynamic and weak noncovalent bonds, which also enables CD DMN and its payloads to diffuse rapidly into the deep skin layer. Moreover, the unique supramolecular structure of CD allows CD DMN to load not only hydrophilic drugs (e.g., rhodamine B as model) but also hydrophobic model drugs (e.g., ibuprofen). As a proof-of-concept, CD DMN loading ibuprofen shows a rapid onset of therapeutic action in a xylene-induced acute inflammation model in mice. This work opens a new avenue for the development of mechanically robust supramolecular DMN and broadens the applications of supramolecular materials. This article is protected by copyright. All rights reserved.

Keywords:  Supramolecular; cyclodextrin; dissolving microneedle; mechanical robustness; transdermal drug delivery

DOI:  https://doi.org/10.1002/adma.202207832
Small. 2022 Oct 03. e2203751

Heparin-Peptide Nanogranules for Thrombosis-Actuated Anticoagulation.

Atip Lawanprasert, Sopida Pimcharoen, Sarah E Sumner, Connor T Watson, Keefe B Manning, Girish S Kirimanjeswara, Scott H Medina.

  Despite nearly a century of clinical use as a blood thinner, heparin's rapid serum clearance and potential to induce severe bleeding events continue to urge the development of more effective controlled delivery strategies. Subcutaneous depots that steadily release the anticoagulant into circulation represent a promising approach to reducing overdose frequency, sustaining therapeutic concentrations of heparin in plasma, and prolonging anticoagulant activity in a safe and effective manner. Subcutaneously deliverable heparin-peptide nanogranules that allow for long-lasting heparin bioavailability in the circulatory system, while enabling on-demand activation of heparin's anticoagulant effects in the thrombus microenvironment, are reported. Biophysical studies demonstrate this responsive behavior is due to the sequestration of heparin within self-assembling peptide nanofibrils and its mechanically actuated decoupling to elicit antithrombotic effects at the clotting site. In vivo studies show these unique properties converge to allow subcutaneous nanogranule depots to extend heparin serum concentrations for an order of magnitude longer than standard dosing regimens while enabling prolonged and controlled anticoagulant activity. This biohybrid delivery system demonstrates a potentially scalable platform for the development of safer, easier to administer, and more effective antithrombotic nanotechnologies.

Keywords:  heparin; nanoparticles; peptides; self-assembly; thrombosis

DOI:  https://doi.org/10.1002/smll.202203751
ACS Nano. 2022 Oct 03.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Chaojie Yu, Zhiwei Yue, Mingyue Shi, Lijie Jiang, Shuang Chen, Mengmeng Yao, Qingyu Yu, Xiaojun Wu, Hong Zhang, Fanglian Yao, Changyong Wang, Hong Sun, Junjie Li.

  Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.

Keywords:  conducting polymer; injectable hydrogel; mechanical−electrical coupling; myocardial repair; tissue engineering

DOI:  https://doi.org/10.1021/acsnano.2c05168
Adv Healthc Mater. 2022 Oct 08. e2201565

Light-programmable Nanocomposite Hydrogel for State-switchable Wound Healing Promotion and Bacterial Infection Elimination.

Zhekun Zhang, Juning Xie, Jun Xing, Changhao Li, Tak Man Wong, Hui Yu, Yuanxing Li, Fabang Yang, Yu Tian, Huan Zhang, Wei Li, Chengyun Ning, Xiaolan Wang, Peng Yu.

  Developing an ideal wound dressing that not only accelerates wound healing but also eliminates potential bacterial infections remains a difficult balancing act. This work reports the design of a light-programmable sodium alginate nanocomposite hydrogel loaded with BiOCl/Polypyrrole nanosheets for state-switchable wound healing promotion and bacterial infection elimination remotely. The nanocomposite hydrogel possesses programmable photoelectric or photothermal conversion due to the expanded light absorption range, optimized electron transmission interface, promoted photo-generated charge separation and transfer of the BiOCl/Polypyrrole nanosheets. Under white light irradiation state, the nanocomposite hydrogel induces human umbilical vein endothelial cells migration and angiogenesis, and accelerates the healing efficiency of mouse skin in vivo. Under NIR light irradiation state, the nanocomposite hydrogel presents superior antibacterial capability in vitro, and reaches an antibacterial rate of 99.1% for S. aureus infected skin wound in vivo. This light-programmable nanocomposite hydrogel provides an on-demand resolution of biological state-switching to balance wound healing and elimination of bacterial infection. This article is protected by copyright. All rights reserved.

Keywords:  bacterial infection; light-programmable; photoelectric; photothermal; wound healing

DOI:  https://doi.org/10.1002/adhm.202201565
Adv Healthc Mater. 2022 Oct 02. e2201671

Bioinspired and Inflammation-modulatory Glycopeptide Hydrogels for Radiation-induced Chronic Skin Injury Repair.

Zujian Feng, Yumin Zhang, Chunfang Yang, Xiang Liu, Yini Huangfu, Chuangnian Zhang, Pingsheng Huang, Anjie Dong, Jinjian Liu, Jianfeng Liu, Deling Kong, Weiwei Wang.

  Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and the concomitant repetitive inflammatory microenvironment caused by imbalance in macrophage homeostasis. Herein, a cutaneous extracellular matrix (ECM)-inspired glycopeptide hydrogel (GK@TAgel ) is rationally designed for accelerating wound healing through modulating the chronic inflammation in RSI. The glycopeptide hydrogel not only replicates ECM-like glycoprotein components and nanofibrous architecture, but also displays effective ROS scavenging and radioprotective capability that could reduce the acute injuries after exposing to irradiation. Importantly, the mannose receptor (MR) in GK@TAgel exhibits high affinity and bioactivity to drive the M2 macrophages polarization, thereby overcoming the persistent inflammatory microenvironment in chronic RSI. The repair of RSI in mice demonstrated GK@TAgel significantly reduced the hyperplasia of epithelial, promoted appendages regeneration and angiogenesis, and decreased the proinflammatory cytokine expression, which was superior over the treatment of commercial radioprotective drug amifostine. Collectively, the ECM-mimetic hydrogel dressing can protect the tissue from irradiation and heal the chronic wound in RSI, holding great potential in clinical wound management and tissue regeneration. This article is protected by copyright. All rights reserved.

Keywords:  Chronic wound healing; Glycopeptide hydrogel; Immunomodulation; Macrophages polarization; ROS scavenging; Radiation-induced skin injury

DOI:  https://doi.org/10.1002/adhm.202201671
Adv Mater. 2022 Oct 03. e2206779

Self-Propelled Nanomotors with Alloyed Engine for Emergency Rescue of Traumatic Brain Injury.

Heping Wang, Xi Chen, Yilin Qi, Chunxiao Wang, Liwen Huang, Ran Wang, Jiamin Li, Xihan Xu, Yutong Zhou, Yang Liu, Xue Xue.

  In severe traumatic brain injury (sTBI), acute oxidative stress and inflammatory cascades rapidly spread to cause irreversible brain damage and low survival rate within minutes. Therefore, developing feasible solution for the quick-treatment of life-threatening emergency is urgently demanded to earn time for hospital treatment. We herein carefully constructed Janus catalysis-driven nanomotors (JCNs) via plasma-induced alloying technology and sputtering-caused half coating strategy. The theoretical calculation and experiment results indicated that heteroatom-doping alloyed engine endowed JCNs much higher catalytic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS) than common Pt-based engine. When JCNs were dropped to the surface of ruptured skull, they can effectively catalyze endogenous hydrogen peroxide, which induces movement as fuels to promote JCNs to deep brain lesions for further nanocatalysts-mediated cascade-blocking therapy (CBT). Results demonstrated that JCNs successfully blocked the inflammatory cascades, thereby reversing multiple behavioral defects and dramatically declining the mortality of sTBI mice. Together, this work provides a revolutionary nanomotors-based strategy to sense brain injury and scavenge oxidative stress. Meanwhile, our JCNs provide a feasible strategy to adapt various first aid scenarios due to their self-propelled movement combined with highly multienzymes-like catalytic activity, exhibiting tremendous therapeutic potential to help people for emergency pretreatment. This article is protected by copyright. All rights reserved.

Keywords:  catalytic therapy; nanomotor; oxidative stress; self-propulsion; traumatic brain injury

DOI:  https://doi.org/10.1002/adma.202206779
Nat Commun. 2022 Oct 03. 13(1): 5802

Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.

Faith Conroy, Rachael Miller, Julia F Alterman, Matthew R Hassler, Dimas Echeverria, Bruno M D C Godinho, Emily G Knox, Ellen Sapp, Jaquelyn Sousa, Ken Yamada, Farah Mahmood, Adel Boudi, Kimberly Kegel-Gleason, Marian DiFiglia, Neil Aronin, Anastasia Khvorova, Edith L Pfister.

Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS, enabling development of CNS-targeted therapeutics. Many genetically-defined neurodegenerative disorders are dominant, favoring selective silencing of the mutant allele. In some cases, successfully targeting the mutant allele requires targeting single nucleotide polymorphism (SNP) heterozygosities. Here, we use Huntington's disease (HD) as a model. The optimized compound exhibits selective silencing of mutant huntingtin protein in patient-derived cells and throughout the HD mouse brain, demonstrating SNP-based allele-specific RNAi silencing of gene expression in vivo in the CNS. Targeting a disease-causing allele using RNAi-based therapies could be helpful in a range of dominant CNS disorders where maintaining wild-type expression is essential.

DOI: https://doi.org/10.1038/s41467-022-33061-x
J Control Release. 2022 Sep 30. pii: S0168-3659(22)00650-2. [Epub ahead of print]

R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer.

Bin Zheng, Zhenghong Liu, Heng Wang, Li Sun, Wing-Fu Lai, Haibao Zhang, Jinxue Wang, Yang Liu, Xiaowen Qin, Xiaolong Qi, Shuai Wang, Youqing Shen, Pu Zhang, Dahong Zhang.

  Intravesical chemotherapy is generally used in the clinic for treating bladder cancer (BCa), but its efficacy is limited due to the permeation barrier and side effects caused by the off-targeting of normal urothelial cells. In this study, BCa cell-derived membrane nanovesicles were used as drug carriers, and their homologous tumor-targeting capacity was utilized. A BCa-targeting hendeca-arginine peptide was functionalized onto the nanovesicles to impart a mucus-penetrating ability and thus overcome the permeation barrier. The tumor-targeting and mucus-penetrating nanovesicles were stable in urine, were highly permeable to the glycosaminoglycan layer, and specifically targeted BCa. The vesicles were internalized through caveolin-mediated endocytosis, were transported to nonlysosome-localized intracellular regions, and efficiently infiltrated bladder tumor spheroids. In in vivo intravesical chemotherapy, the nanovesicles achieved chemo-resection in murine orthotopic BCa models. This BCa-targeting and mucus-penetrating drug delivery system may be promising for the intravesical chemotherapy of BCa.

Keywords:  Bladder cancer; Cell membrane-camouflaged nanoparticle; Intravesical therapy; Mucus-penetrating

DOI:  https://doi.org/10.1016/j.jconrel.2022.09.055
ACS Nano. 2022 Oct 06.

Targeting to Tumor-Harbored Bacteria for Precision Tumor Therapy.

Wen-Fang Song, Diwei Zheng, Si-Min Zeng, Xuan Zeng, Xian-Zheng Zhang.

  The differential tumor environment guides various antitumor drug delivery strategies for efficient cancer treatment. Here, based on the special bacteria-enriched tumor environment, we report a different drug delivery strategy by targeting bacteria inhabiting tumor sites. With a tissue microarray analysis, it was found that bacteria amounts displayed significant differences between tumor and normal tissues. Bacteria-targeted mesoporous silica nanoparticles decorated with bacterial lipoteichoic acid (LTA) antibody (LTA-MSNs) could precisely target bacteria in tumors and deliver antitumor drugs. By the intravenous administration of bacteria-targeted nanoparticles, we showed in mice with colon cancer, lung cancer, and breast cancer that LTA-MSNs exhibited a high tumor-targeting ability. As a proof-of-concept study, tumor microbes as some of the characteristics of a tumor environment could be utilized as potential targets for tumor targeting. This bacteria-guided tumor-targeting strategy might have great potential in differential drug delivery and cancer treatment.

Keywords:  bacterial inhabitation; drug delivery; mesoporous silica nanoparticle; tumor microbe; tumor target

DOI:  https://doi.org/10.1021/acsnano.2c08555
Nat Commun. 2022 Oct 05. 13(1): 5875

3D-printed microrobots from design to translation.

Sajjad Rahmani Dabbagh, Misagh Rezapour Sarabi, Mehmet Tugrul Birtek, Siamak Seyfi, Metin Sitti, Savas Tasoglu.

Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.

DOI: https://doi.org/10.1038/s41467-022-33409-3
Adv Healthc Mater. 2022 Oct 03. e2202114

Acellularized Uvea Hydrogel As Novel Injectable Platform for Cell-based Delivering Treatment of Retinal Degeneration and Optimizing Retinal Organoids Inducible System.

Guilan Li, Sheng Liu, Wenfei Chen, Zhijian Jiang, Yuanting Luo, Dongliang Wang, Yingfeng Zheng, Yizhi Liu.

  Replenishing the retina with retinal pigment epithelial (RPE) cells derived from pluripotent stem cells (PSCs) has great promise for treating retinal degenerative diseases, but it is limited by poor cell survival and integration in vivo. Herein, porcine acellular sclera and uvea extracellular matrix (ECM) and their counterpart hydrogels are developed, and their effects on the biological behavior of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) and embryoid body (hiPSC-EB) differentiation are investigated. Both acellular ECM hydrogels have excellent biocompatibility and suitable biodegradability without evoking an obvious immune response. Most importantly, the decellularized uvea hydrogel (U-Gel)-delivered cells injection remarkably promotes hiPSC-RPE cells survival and integration in the subretinal space, rescues photoreceptor cells death and retinal gliosis, and restores vision in rats with retinal degeneration for a long duration. In addition, medium supplementation with decellularized uvea peptides promotes hiPSC-EBs onset morphogenesis and neural/retinal differentiation, forming layered retinal organoids. This study demonstrates that ECM hydrogel-delivered hiPSC-RPE cells injection may be a useful approach for treating retinal degeneration disease, combining with an optimized retinal seeding cells induction program, which has potential for clinical application. This article is protected by copyright. All rights reserved.

Keywords:  Decellularized extracellular matrix; Injectable hydrogel; Retinal degeneration; Retinal organoids; hiPSC-RPE cells

DOI:  https://doi.org/10.1002/adhm.202202114
Adv Mater. 2022 Oct 03. e2204257

Multifunctional 4D-printed Sperm-hybrid Microcarriers for Assisted Reproduction.

Fatemeh Rajabasadi, Silvia Moreno, Kristin Fichna, Azaam Aziz, Dietmar Appelhans, Oliver G Schmidt, Mariana Medina-Sánchez.

  Remotely controllable microrobots are appealing for various biomedical in vivo applications. In particular, our group has focused in the last years in developing sperm-microcarriers to assist sperm cells with motion deficiencies or low count (two of the most prominent male infertility problems) to reach the oocyte towards in vivo assisted fertilization. Different sperm carriers considering their motion in realistic media and confined environments have been optimized. However, the already reported sperm carriers have been mainly designed to transport single sperm cells, with limited functionality. Thus, to take a step forward, here we propose the development of a 4D-printed multifunctional microcarrier containing soft and smart materials, which can not only transport and deliver multiple sperm cells, but also release heparin and mediate local enzymatic reactions by hyaluronidase-loaded polymersomes (HYAL-Psomes). These multifunctional facets enable in-situ (i) sperm capacitation/hyperactivation, and (ii) local degradation of the cumulus complex that surrounds the oocyte, both to facilitate the sperm-oocyte interaction for the ultimate goal of in vivo assisted fertilization. This article is protected by copyright. All rights reserved.

Keywords:  4D-printing lithography; assisted fertilization; biohybrid micromotors; enzyme-loaded polymersomes; multifunctional sperm-hybrid microcarriers; targeted cargo-delivery

DOI:  https://doi.org/10.1002/adma.202204257
Nano Lett. 2022 Oct 04.

Size-Controllable and Self-Assembled DNA Nanosphere for Amplified MicroRNA Imaging through ATP-Fueled Cyclic Dissociation.

Jiaoli Wang, Juan Li, Yu Chen, Ruiting Liu, Yixuan Wu, Jianbo Liu, Xiaohai Yang, Kemin Wang, Jin Huang.

  Visualizing intracellular microRNA (miRNA) is of great importance for revealing its roles in the development of disease. However, cell membrane barrier, complex intracellular environment and low abundance of target miRNA are three main challenges for efficient imaging of intracellular miRNA. Here, we report a size-controllable and self-assembled DNA nanosphere with ATP-fueled dissociation property for amplified miRNA imaging in live cells and mice. The DNA nanosphere was self-assembled from Y-shaped DNA (Y-DNA) monomers through predesigned base pair hybridization, and the size could be easily controlled by varying the concentration of Y-DNA. Once the nanosphere was internalized into cells, the intracellular specific target miRNA would trigger the cyclic dissociation of the DNA nanosphere driven by ATP, resulting in amplified FRET signal. The programmable DNA nanosphere has been proven to work well for detecting the expression of miRNA in cancer cells and in mice, which demonstrates its fairish cell penetration, stability and sensitivity.

Keywords:  ATP; DNA nanosphere; cancer cells; fluorescence imaging; miRNA

DOI:  https://doi.org/10.1021/acs.nanolett.2c02934
Adv Mater. 2022 Oct 03. e2205881

Self-powered, Implantable, and Wirelessly-Controlled NO Generation System for Intracranial Neuroglioma Therapy.

Shuncheng Yao, Minjia Zheng, Zhuo Wang, Yunchao Zhao, Shaobo Wang, Zhirong Liu, Zhou Li, Yunqian Guan, Zhong Lin Wang, Linlin Li.

  Gas therapy has been emerging technology for improving cancer therapy with high efficiency and low side effects. However, due to the existence of the gatekeeper of blood - brain barrier (BBB) and limited availability of current drug delivery systems, there still have no reports on gas therapy for intracranial neuroglioma. Herein, we report an integrated, self-powered and wirelessly-controlled gas therapy system composed of a self-powered triboelectric nanogenerator (TENG) and implantable nitric oxide (NO) releasing device for intracranial neuroglioma therapy. In the system, the patient self-driven TENG converts the mechanical energy of body movements into electricity as a sustainable and self-controlled power source. When delivering the energy to lighten LED light in the implantable NO releasing device via wireless control, the encapsulated NO donor s-nitrosoglutathione (GSNO) can generate NO gas to locally kill the glioma cells. We verify the efficacy of the proof-of-concept system in subcutaneous 4T1 breast cancer model in mice and intracranial glioblastoma multiforme in rats. This self-powered gas therapy system has great potential to be an effective adjuvant treatment modality to inhibit tumor growth, relapse, and invasion via teletherapy. This article is protected by copyright. All rights reserved.

Keywords:  gas therapy; implantable; neuroglioma; self-powered; wireless control

DOI:  https://doi.org/10.1002/adma.202205881
Nat Commun. 2022 Oct 07. 13(1): 5907

Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer.

Edward M Kennedy, Agnieszka Denslow, Jacqueline Hewett, Lingxin Kong, Ana De Almeida, Jeffrey D Bryant, Jennifer S Lee, Judy Jacques, Sonia Feau, Melissa Hayes, Elizabeth L McMichael, Daniel Wambua, Terry Farkaly, Amal A Rahmeh, Lauren Herschelman, Danielle Douglas, Jacob Spinale, Sanmit Adhikari, Jessica Deterling, Matt Scott, Brian B Haines, Mitchell H Finer, Ted T Ashburn, Christophe Quéva, Lorena Lerner.

The therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21, we demonstrate vRNA delivery and replication, virus assembly, spread and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream. Synthetic-SVV replication in tumors promotes immune cell infiltration, remodeling of the tumor microenvironment, and enhances the activity of anti-PD-1 checkpoint inhibitor. In mouse and non-human primates, Synthetic-SVV is well tolerated reaching exposure well above the requirement for anti-tumor activity. Altogether, the Synthetic RNA virus platform provides an approach that enables repeat intravenous administration of viral immunotherapy.

DOI: https://doi.org/10.1038/s41467-022-33599-w
Drug Deliv Transl Res. 2022 Oct 07.

Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins.

Bettina Gabold, Friederike Adams, Sophie Brameyer, Kirsten Jung, Christian L Ried, Thomas Merdan, Olivia M Merkel.

  Nose-to-brain delivery presents a promising alternative route compared to classical blood-brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide-alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110-150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air-liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity.

Keywords:  Brain delivery; Chitosan nanoparticles; Glioblastoma; Nose-to-brain; Transferrin receptor

DOI:  https://doi.org/10.1007/s13346-022-01245-z