bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–06–30
eleven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Engineering Approaches for Exosome Cargo Loading and Targeted Delivery: Biological versus Chemical Perspectives.
  2. Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.
  3. From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine.
  4. Advances in bacteria-based drug delivery systems for anti-tumor therapy.
  5. Chinese hamster ovary cell line engineering strategies for modular production of custom extracellular vesicles.
  6. Exosomes, and the potential for exosome-based interventions against COVID-19.
  7. Therapeutic Effects of Engineered Exosomes from RAW264.7 Cells Overexpressing hsa-let-7i-5p against Sepsis in Mice-A Comparative Study with Human Placenta-Derived Mesenchymal Stem Cell Exosomes.
  8. Engineering extracellular vesicles for ROS scavenging and tissue regeneration.
  9. Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs.
  10. Interplay between Wnt signaling molecules and exosomal miRNAs in breast cancer (Review).
  11. Nanoengineering Solutions for Cancer Therapy: Bridging the Gap between Clinical Practice and Translational Research.
  1. ACS Biomater Sci Eng. 2024 Jun 28.
    Engineering Approaches for Exosome Cargo Loading and Targeted Delivery: Biological versus Chemical Perspectives.
    Waqas Ahmed, Asim Mushtaq, Shahzad Ali, Nawaz Khan, Yujie Liang, Li Duan.
      Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.
    Keywords:  biological engineering; cargo loading; chemical engineering; exosomes; targeted delivery
    DOI:  https://doi.org/10.1021/acsbiomaterials.4c00856
  2. Pharmaceutics. 2024 May 24. pii: 709. [Epub ahead of print]16(6):
    Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.
    Anu Sharma, Anita Yadav, Aparajita Nandy, Subhadip Ghatak.
      Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice.
    Keywords:  EV-based therapeutics regulatory affairs; FDA; cell–cell crosstalk; exosome therapy; precision medicine; regenerative medicine
    DOI:  https://doi.org/10.3390/pharmaceutics16060709
  3. Cytotechnology. 2024 Aug;76(4): 363-401
    From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine.
    Gajanan Arbade, Jovel Varghese Jose, Arvind Gulbake, Sachin Kadam, Shivaji B Kashte.
      In the fields of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have become viable therapeutic tools. EVs produced from stem cells promote tissue healing by regulating the immune system, enhancing cell proliferation and aiding remodeling processes. Recently, EV has gained significant attention from researchers due to its ability to treat various diseases. Unlike stem cells, stem cell-derived EVs show lower immunogenicity, are less able to overcome biological barriers, and have a higher safety profile. This makes the use of EVs derived from cell-free stem cells a promising alternative to whole-cell therapy. This review focuses on the biogenesis, isolation, and characterization of EVs and highlights their therapeutic potential for bone fracture healing, wound healing, and neuronal tissue repair and treatment of kidney and intestinal diseases. Additionally, this review discusses the potential of EVs for the treatment of cancer, COVID-19, and HIV. In summary, the use of EVs derived from stem cells offers a new horizon for applications in tissue engineering and regenerative medicine.
    Keywords:  Cell free therapy; Disease management; Exosomes; Extracellular vesicles; Stem cells; Tissue engineering
    DOI:  https://doi.org/10.1007/s10616-024-00631-4
  4. Clin Transl Immunology. 2024 ;13(7): e1518
    Advances in bacteria-based drug delivery systems for anti-tumor therapy.
    Han Shuwen, Song Yifei, Wu Xinyue, Qu Zhanbo, Yu Xiang, Yang Xi.
      In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti-tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria-based drug delivery systems for anti-tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria-based drug systems.
    Keywords:  anti‐tumor; bacteria; drug delivery system; synthetic biology
    DOI:  https://doi.org/10.1002/cti2.1518
  5. Biotechnol Bioeng. 2024 Jun 25.
    Chinese hamster ovary cell line engineering strategies for modular production of custom extracellular vesicles.
    Braulio Carrillo Sanchez, Matthew Hinchliffe, Mark Ellis, Catherine Simpson, David Humphreys, Bernie Sweeney, Daniel G Bracewell.
      Continuously secreted by all cell types, extracellular vesicles (EVs) are small membrane-bound structures which shuttle bioactive cargo between cells across their external environment. Their central role as natural molecular messengers and ability to cross biological barriers has garnered significant attention in the use of EVs as therapeutic delivery vehicles. Still, harnessing the potential of EVs is faced with many obstacles. A cell line engineering approach can be used to exploit EVs to encapsulate a bespoke cargo of interest. However, full details regarding native EV-loading mechanisms remain under debate, making this a challenge. While Chinese hamster ovary (CHO) cells are well known to be the preferred host for recombinant therapeutic protein production, their application as an EV producer cell host has been largely overlooked. In this study, we engineered CHO DG44 cells to produce custom EVs with bespoke cargo. To this end, genetic constructs employing split green fluorescent protein technology were designed for tagging both CD81 and protein cargoes to enable EV loading via self-assembling activity. To demonstrate this, NanoLuc and mCherry were used as model reporter cargoes to validate engineered loading into EVs. Experimental findings indicated that our custom EV approach produced vesicles with up to 15-fold greater cargo compared with commonly used passive loading strategies. When applied to recipient cells, we observed a dose-dependent increase in cargo activity, suggesting successful delivery of engineered cargo via our custom CHO EVs.
    Keywords:  CHO cells; cell line engineering; delivery vehicle; exosomes; extracellular vesicles; genetic constructs
    DOI:  https://doi.org/10.1002/bit.28776
  6. Rev Med Virol. 2024 Jul;34(4): e2562
    Exosomes, and the potential for exosome-based interventions against COVID-19.
    Abolfazl Rahmani, Ali Soleymani, Mustafa Almukhtar, Kimia Behzad Moghadam, Zahra Vaziri, Ali Hosein Tabar Kashi, Reza Adabi Firoozjah, Mehrdad Jafari Tadi, Maryam Zolfaghari Dehkharghani, Hadi Valadi, Ali Akbar Moghadamnia, Robin B Gasser, Ali Rostami.
      Since late 2019, the world has been devastated by the coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with more than 760 million people affected and ∼seven million deaths reported. Although effective treatments for COVID-19 are currently limited, there has been a strong focus on developing new therapeutic approaches to address the morbidity and mortality linked to this disease. An approach that is currently being investigated is the use of exosome-based therapies. Exosomes are small, extracellular vesicles that play a role in many clinical diseases, including viral infections, infected cells release exosomes that can transmit viral components, such as miRNAs and proteins, and can also include receptors for viruses that facilitate viral entry into recipient cells. SARS-CoV-2 has the ability to impact the formation, secretion, and release of exosomes, thereby potentially facilitating or intensifying the transmission of the virus among cells, tissues and individuals. Therefore, designing synthetic exosomes that carry immunomodulatory cargo and antiviral compounds are proposed to be a promising strategy for the treatment of COVID-19 and other viral diseases. Moreover, exosomes generated from mesenchymal stem cells (MSC) might be employed as cell-free therapeutic agents, as MSC-derived exosomes can diminish the cytokine storm and reverse the suppression of host anti-viral defences associated with COVID-19, and boost the repair of lung damage linked to mitochondrial activity. The present article discusses the significance and roles of exosomes in COVID-19, and explores potential future applications of exosomes in combating this disease. Despite the challenges posed by COVID-19, exosome-based therapies could represent a promising avenue for improving patient outcomes and reducing the impact of this disease.
    Keywords:  COVID‐19; SARS‐CoV‐2; biology; diagnosis; exosome; host‐pathogen interplay; mesenchymal stem cells; treatment; vaccine
    DOI:  https://doi.org/10.1002/rmv.2562
  7. J Pers Med. 2024 Jun 09. pii: 619. [Epub ahead of print]14(6):
    Therapeutic Effects of Engineered Exosomes from RAW264.7 Cells Overexpressing hsa-let-7i-5p against Sepsis in Mice-A Comparative Study with Human Placenta-Derived Mesenchymal Stem Cell Exosomes.
    Van Long Le, Chao-Yuan Chang, Ching-Wei Chuang, Syuan-Hao Syu, Hung-Jen Shih, Hong-Phuc Nguyen Vo, Minh Nguyen Van, Chun-Jen Huang.
      This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.
    Keywords:  Raw264.7 cells; endotoxin; exosomes; hsa-let-7i-5p; lung; mice; stem cells
    DOI:  https://doi.org/10.3390/jpm14060619
  8. Nano Converg. 2024 Jun 26. 11(1): 24
    Engineering extracellular vesicles for ROS scavenging and tissue regeneration.
    Ahmed Abdal Dayem, Ellie Yan, Minjae Do, Yoojung Kim, Yeongseo Lee, Ssang-Goo Cho, Deok-Ho Kim.
      Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative, extracellular vesicles (EVs) derived from stem cells exhibit remarkable abilities to activate critical signaling cascades, thereby facilitating tissue repair. EVs, nano-scale membrane vesicles, mediate intercellular communication by encapsulating a diverse cargo of proteins, lipids, and nucleic acids. Their therapeutic potential lies in delivering cargos, activating signaling pathways, and efficiently mitigating oxidative stress-an essential aspect of overcoming limitations in stem cell-based tissue repair. This review focuses on engineering and applying EVs in tissue regeneration, emphasizing their role in regulating reactive oxygen species (ROS) pathways. Additionally, we explore strategies to enhance EV therapeutic activity, including functionalization and incorporation of antioxidant defense proteins. Understanding these molecular mechanisms is crucial for optimizing EV-based regenerative therapies. Insights into EV and ROS signaling modulation pave the way for targeted and efficient regenerative therapies harnessing the potential of EVs.
    Keywords:  Biomaterial scaffold; Extracellular vesicles; Reactive oxygen species scavenging; Tissue regeneration; miRNA delivery
    DOI:  https://doi.org/10.1186/s40580-024-00430-9
  9. Pharmaceutics. 2024 May 29. pii: 734. [Epub ahead of print]16(6):
    Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs.
    Santu Sarkar, Sezgin Kiren, William H Gmeiner.
      Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To provide further advances in therapeutic efficacy, next-generation prodrugs and nanodelivery systems for FPs are being developed. This review focuses on recent innovative nanodelivery approaches for FP drugs that display therapeutic promise. We summarize established, clinically useful FP prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression for optimal anticancer activity. We then describe the use of FP DNA-based polymers (e.g., CF10) for the delivery of activated FP nucleotides as a nanodelivery approach with proven activity in pre-clinical models and with clinical potential. Multiple nanodelivery systems for FP delivery show promise in CRC pre-clinical models and we review advances in albumin-mediated FP delivery, the development of mesoporous silica nanoparticles, emulsion-based nanoparticles, metal nanoparticles, hydrogel-based delivery, and liposomes and lipid nanoparticles that display particular promise for therapeutic development. Nanodelivery of FPs is anticipated to impact CRC treatment in the coming years and to improve survival for cancer patients.
    Keywords:  colorectal cancer; fluoropyrimidine; nanodelivery; prodrug; thymidylate synthase
    DOI:  https://doi.org/10.3390/pharmaceutics16060734
  10. Oncol Rep. 2024 Aug;pii: 107. [Epub ahead of print]52(2):
    Interplay between Wnt signaling molecules and exosomal miRNAs in breast cancer (Review).
    Hailong Li, Xia Li, Wei Du.
      Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial‑mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.
    Keywords:  Wnt signaling; breast cancer; diagnostic biomarkers; exosomal microRNAs
    DOI:  https://doi.org/10.3892/or.2024.8766
  11. J Clin Med. 2024 Jun 13. pii: 3466. [Epub ahead of print]13(12):
    Nanoengineering Solutions for Cancer Therapy: Bridging the Gap between Clinical Practice and Translational Research.
    Pankaj Garg, Siddhika Pareek, Prakash Kulkarni, Ravi Salgia, Sharad S Singhal.
      Nanoengineering has emerged as a progressive method in cancer treatment, offering precise and targeted delivery of therapeutic agents while concurrently reducing overall toxicity. This scholarly article delves into the innovative strategies and advancements in nanoengineering that bridge the gap between clinical practice and research in the field of cancer treatment. Various nanoengineered platforms such as nanoparticles, liposomes, and dendrimers are scrutinized for their capacity to encapsulate drugs, augment drug efficacy, and enhance pharmacokinetics. Moreover, the article investigates research breakthroughs that drive the progression and enhancement of nanoengineered remedies, encompassing the identification of biomarkers, establishment of preclinical models, and advancement of biomaterials, all of which are imperative for translating laboratory findings into practical medical interventions. Furthermore, the integration of nanotechnology with imaging modalities, which amplify cancer detection, treatment monitoring, and response assessment, is thoroughly examined. Finally, the obstacles and prospective directions in nanoengineering, including regulatory challenges and issues related to scalability, are examined. This underscores the significance of fostering collaboration among various entities in order to efficiently translate nanoengineered interventions into enhanced cancer therapies and patient management.
    Keywords:  clinical practice; nanoengineering; preclinical models; targeted delivery; translational research
    DOI:  https://doi.org/10.3390/jcm13123466
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