bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–06–09
eightteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exploring the clinical transition of engineered exosomes designed for intracellular delivery of therapeutic proteins.
  2. Advances in nanobubbles for cancer theranostics: Delivery, imaging and therapy.
  3. Organoids as a new approach for improving pediatric cancer research.
  4. A comprehensive review of engineered exosomes from the preparation strategy to therapeutic applications.
  5. Plant-derived Exosomes: Pioneering Breakthroughs in Therapeutics, Targeted Drug Delivery, and Regenerative Medicine.
  6. Unlocking the Medicinal Potential of Plant-Derived Extracellular Vesicles: current Progress and Future Perspectives.
  7. Lipid nanoparticles-based RNA therapies for breast cancer treatment.
  8. Nanotherapeutics targeting autophagy regulation for improved cancer therapy.
  9. Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy.
  10. Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications.
  11. Engineered Exosomes Containing microRNA-29b-2 and Targeting the Somatostatin Receptor Reduce Presenilin 1 Expression and Decrease the β-Amyloid Accumulation in the Brains of Mice with Alzheimer's Disease.
  12. The future of cancer therapy: exploring the potential of patient-derived organoids in drug development.
  13. Factors affecting response variables with emphasis on drug release and loading for optimization of liposomes.
  14. Extracellular Vesicles in Cardiovascular Pathophysiology: Communications, Biomarkers, and Therapeutic Potential.
  15. The involvement and application potential of exosomes in breast cancer immunotherapy.
  16. Exosome-based anticancer vaccines: From Bench to Bedside.
  17. Revolutionizing Lung Cancer Treatment: Innovative CRISPR-Cas9 Delivery Strategies.
  18. Role and therapeutic perspectives of extracellular vesicles derived from liver and adipose tissue in metabolic dysfunction-associated steatotic liver disease.
  1. Stem Cells Transl Med. 2024 Jun 05. pii: szae027. [Epub ahead of print]
    Exploring the clinical transition of engineered exosomes designed for intracellular delivery of therapeutic proteins.
    Minseong Kim, Hojun Choi, Deok-Jin Jang, Hye-Jung Kim, Yujin Sub, Heon Yung Gee, Chulhee Choi.
      Extracellular vesicles, particularly exosomes, have emerged as promising drug delivery systems owing to their unique advantages, such as biocompatibility, immune tolerability, and target specificity. Various engineering strategies have been implemented to harness these innate qualities, with a focus on enhancing the pharmacokinetic and pharmacodynamic properties of exosomes via payload loading and surface engineering for active targeting. This concise review outlines the challenges in the development of exosomes as drug carriers and offers insights into strategies for their effective clinical translation. We also highlight preclinical studies that have successfully employed anti-inflammatory exosomes and suggest future directions for exosome therapeutics. These advancements underscore the potential for integrating exosome-based therapies into clinical practice, heralding promise for future medical interventions.
    Keywords:  drug delivery system; exosome purification; exosomes; extracellular vesicles; inflammation; protein therapeutics
    DOI:  https://doi.org/10.1093/stcltm/szae027
  2. Biochem Pharmacol. 2024 Jun 05. pii: S0006-2952(24)00324-1. [Epub ahead of print] 116341
    Advances in nanobubbles for cancer theranostics: Delivery, imaging and therapy.
    Liu Na, Fan Fan.
      Maximizing treatment efficacy and forecasting patient prognosis in cancer necessitates the strategic use of targeted therapy, coupled with the prompt precise detection of malignant tumors. Theutilizationof gaseous systems as an adaptable platform for creating nanobubbles (NBs) has garnered significant attention as theranostics, which involve combining contrast chemicals typically used for imaging with pharmaceuticals to diagnose and treattumorssynergistically in apersonalizedmanner for each patient. This review specifically examines the utilization of oxygen NBsplatforms as a theranostic weapon in the field of oncology. We thoroughly examine the key factors that impact the effectiveness of NBs preparations and the consequences of these treatment methods. This review extensively examines recent advancements in composition schemes, advanced developments in pre-clinical phases, and other groundbreaking inventions in the area of NBs. Moreover, this review offers a thorough examination of the optimistic future possibilities, addressing prospective methods for improvement and incorporation into widely accepted therapeutic practices. As we explore the ever-changing field of cancer theranostics, the incorporation of oxygen NBs appears as a promising development, providing new opportunities for precision medicine and marking a revolutionary age in cancer research and therapy.
    Keywords:  Cancer theranostics; Drug delivery; NBs; Nanomedicine; Precision medicine; Targeted therapy; Tumor imaging; oxygen NBs
    DOI:  https://doi.org/10.1016/j.bcp.2024.116341
  3. Front Oncol. 2024 ;14 1414311
    Organoids as a new approach for improving pediatric cancer research.
    Silvia Lampis, Angela Galardi, Virginia Di Paolo, Angela Di Giannatale.
      A key challenge in cancer research is the meticulous development of models that faithfully emulates the intricacies of the patient scenario, with emphasis on preserving intra-tumoral heterogeneity and the dynamic milieu of the tumor microenvironment (TME). Organoids emerge as promising tool in new drug development, drug screening and precision medicine. Despite advances in the diagnoses and treatment of pediatric cancers, certain tumor subtypes persist in yielding unfavorable prognoses. Moreover, the prognosis for a significant portion of children experiencing disease relapse is dismal. To improve pediatric outcome many groups are focusing on the development of precision medicine approach. In this review, we summarize the current knowledge about using organoid system as model in preclinical and clinical solid-pediatric cancer. Since organoids retain the pivotal characteristics of primary parent tumors, they exert great potential in discovering novel tumor biomarkers, exploring drug-resistance mechanism and predicting tumor responses to chemotherapy, targeted therapy and immunotherapies. We also examine both the potential opportunities and existing challenges inherent organoids, hoping to point out the direction for future organoid development.
    Keywords:  3D models; cancer modeling; pediatric cancer; precision medicine; tumor organoids
    DOI:  https://doi.org/10.3389/fonc.2024.1414311
  4. Biomater Sci. 2024 Jun 03.
    A comprehensive review of engineered exosomes from the preparation strategy to therapeutic applications.
    Xiying Fan, Yiwen Zhang, Wenshuai Liu, Mingzheng Shao, Yibo Gong, Tingya Wang, Song Xue, Rui Nian.
      Exosomes exhibit high bioavailability, biological stability, targeted specificity, low toxicity, and low immunogenicity in shuttling various bioactive molecules such as proteins, lipids, RNA, and DNA. Natural exosomes, however, have limited production, targeting abilities, and therapeutic efficacy in clinical trials. On the other hand, engineered exosomes have demonstrated long-term circulation, high stability, targeted delivery, and efficient intracellular drug release, garnering significant attention. The engineered exosomes bring new insights into developing next-generation drug delivery systems and show enormous potential in therapeutic applications, such as tumor therapies, diabetes management, cardiovascular disease, and tissue regeneration and repair. In this review, we provide an overview of recent advancements associated with engineered exosomes by focusing on the state-of-the-art strategies for cell engineering and exosome engineering. Exosome isolation methods, including traditional and emerging approaches, are systematically compared along with advancements in characterization methods. Current challenges and future opportunities are further discussed in terms of the preparation and application of engineered exosomes.
    DOI:  https://doi.org/10.1039/d4bm00558a
  5. Pharm Nanotechnol. 2024 Jun 04.
    Plant-derived Exosomes: Pioneering Breakthroughs in Therapeutics, Targeted Drug Delivery, and Regenerative Medicine.
    Srabona Dutta, Sourav Ghosh, Monosiz Rahaman, Sejuti Ray Chowdhury.
      Small extracellular vesicles called exosomes, which cells release, have drawn a lot of attention recently because of their ability to serve as therapeutic delivery systems for drugs and regenerative medicine applications. The investigation of plant-based exosomes as a cutting-edge platform for drug administration has emerged as an enticing research topic. A summary of the pharmaceutical feasibility of exosomes generated from plants and their uses in drug delivery along with regenerative medicine are the goals of this review study. Plant exosomes can be combined into nanoparticlebased medication delivery systems to increase their stability, targeting, and cargo delivery capabilities. By loading plant exosomes with therapeutic compounds and encapsulating them within nanoparticles, controlled release and targeted distribution to specific cells or tissues may be achieved. In gene therapy, plant exosomes can be modified to carry nucleic acids like plasmid DNA, siRNA, or miRNA. Effective gene delivery and therapeutic gene expression regulation can be accomplished by encasing nucleic acids in exosomes or surface-modifying exosomes to improve their interaction with target cells. In this review, we through the history and features of plant exosomes, examine how they differ from mammalian exosomes, and consider how they may be used for gene therapy, tissue regeneration, and targeted medication delivery. The difficulties and prospects for creating exosomebased plant medicines are also explored.
    Keywords:  Plant exosome; gene therapy; immunomodulation.; targeted drug delivery; therapeutic vesicle
    DOI:  https://doi.org/10.2174/0122117385305245240424093014
  6. Int J Nanomedicine. 2024 ;19 4877-4892
    Unlocking the Medicinal Potential of Plant-Derived Extracellular Vesicles: current Progress and Future Perspectives.
    Xiaoliang Liu, Kecheng Lou, Yunmeng Zhang, Chuanxiao Li, Shenghong Wei, Shangzhi Feng.
      Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.
    Keywords:  Chinese medicine preparation; drug delivery nanoplatforms; nanoparticle; nanotherapeutics; plant-derived extracellular vesicles
    DOI:  https://doi.org/10.2147/IJN.S463145
  7. Drug Deliv Transl Res. 2024 Jun 03.
    Lipid nanoparticles-based RNA therapies for breast cancer treatment.
    Luigia Serpico, Yuewen Zhu, Renata Faria Maia, Sumedha Sumedha, Mohammad-Ali Shahbazi, Hélder A Santos.
      Breast cancer (BC) prevails as a major burden on global healthcare, being the most prevalent form of cancer among women. BC is a complex and heterogeneous disease, and current therapies, such as chemotherapy and radiotherapy, frequently fall short in providing effective solutions. These treatments fail to mitigate the risk of cancer recurrence and cause severe side effects that, in turn, compromise therapeutic responses in patients. Over the last decade, several strategies have been proposed to overcome these limitations. Among them, RNA-based technologies have demonstrated their potential across various clinical applications, notably in cancer therapy. However, RNA therapies are still limited by a series of critical issues like off-target effect and poor stability in circulation. Thus, novel approaches have been investigated to improve the targeting and bioavailability of RNA-based formulations to achieve an appropriate therapeutic outcome. Lipid nanoparticles (LNPs) have been largely proven to be an advantageous carrier for nucleic acids and RNA. This perspective explores the most recent advances on RNA-based technology with an emphasis on LNPs' utilization as effective nanocarriers in BC therapy and most recent progresses in their clinical applications.
    Keywords:  Breast cancer; Clinical applications; Gene therapy; Lipid nanoparticles; RNA technologies
    DOI:  https://doi.org/10.1007/s13346-024-01638-2
  8. Acta Pharm Sin B. 2024 Jun;14(6): 2447-2474
    Nanotherapeutics targeting autophagy regulation for improved cancer therapy.
    Yunmeng Liu, Yaxin Wang, Jincheng Zhang, Qikai Peng, Xingdong Wang, Xiyue Xiao, Kai Shi.
      The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.
    Keywords:  Autophagy regulation; Cancer therapy; Combination strategies; Delivery strategies; Dual effects; Nanomaterials; Nanotherapeutic; Signal transduction pathway
    DOI:  https://doi.org/10.1016/j.apsb.2024.03.019
  9. Curr Med Chem. 2024 Jun 05.
    Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy.
    Seyed Morteza Naghib, Bahar Ahmadi, M R Mozafari.
      Cancer therapy has seen significant advancements in recent years, with the emergence of RNA interference (RNAi) as a promising strategy for targeted gene silencing. However, the successful delivery of small interfering RNA (siRNA) to cancer cells remains a challenge. Chitosan nanoparticles (CSNPs) can be derived from the natural polysaccharide chitin sources. CSNPs have gained considerable attention as a potential solution to encapsulate siRNA due to their biocompatibility, and biodegradability. This article explores the application of CSNPs for siRNA delivery in cancer therapy. Firstly, it discusses the significance of siRNA in gene regulation and highlights its potential to selectively silence oncogenes or tumor suppressor genes, making it a powerful tool in cancer treatment. The obstacles associated with effective siRNA delivery, such as degradation by nucleases and poor cellular uptake, are also addressed. Next, the focus shifts to the unique properties of CSNPs that make them attractive for siRNA delivery. The discussion revolves around how chitosan can interact electrostatically with siRNA to create stable complexes, as well as the controlled release of siRNA from CSNPs. This controlled release ensures sustained and efficient delivery of siRNA to cancer cells, maximizing therapeutic efficacy. Moreover, the biocompatibility and biodegradability of CSNPs make them ideal for in vivo applications. Different approaches to modifying and functionalizing surfaces are investigated by emphasizing on enhancement of stability and targeting abilities of CSNPs in cancer treatment. Registered trials for CS and siRNA are summarized, along with ongoing investigations into various applications of chitosan in medical treatments. Overall, the application of CSNPs in siRNA delivery for cancer therapy holds great promise and offers a potential solution to overcome the challenges associated with RNAi-based treatments. Continued advancements in this field will likely lead to improved targeted therapies with reduced side effects, ultimately benefitting cancer patients worldwide.
    Keywords:  cancer therapy.; chitosan; gene therapy; nanogel; siRNA; smart drug delivery
    DOI:  https://doi.org/10.2174/0109298673286052240426044945
  10. Front Immunol. 2024 ;15 1401867
    Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications.
    Xuezhi Sun, Wei Li, Li Zhao, Ke Fan, Fenfen Qin, Liwen Shi, Feng Gao, Chunlan Zheng.
      Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell-cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB.
    Keywords:  diagnosis; exosome; extracellular vesicles; immune regulation; therapeutic applications; tuberculosis
    DOI:  https://doi.org/10.3389/fimmu.2024.1401867
  11. Int J Nanomedicine. 2024 ;19 4977-4994
    Engineered Exosomes Containing microRNA-29b-2 and Targeting the Somatostatin Receptor Reduce Presenilin 1 Expression and Decrease the β-Amyloid Accumulation in the Brains of Mice with Alzheimer's Disease.
    En-Yi Lin, Shao-Xi Hsu, Bing-Hua Wu, Yu-Chen Deng, Wei Wuli, Yuan-Sheng Li, Jui-Hao Lee, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou.
       Purpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects.
    Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the β-amyloid accumulation for Alzheimer's disease (AD) in vitro and in vivo.
    Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model.
    Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.
    Keywords:  3xTG-AD; SH-SY5Y; functional nanocarriers; hippocampus; oligonucleotide drug
    DOI:  https://doi.org/10.2147/IJN.S442876
  12. Front Cell Dev Biol. 2024 ;12 1401504
    The future of cancer therapy: exploring the potential of patient-derived organoids in drug development.
    Cigir Biray Avci, Bakiye Goker Bagca, Behrouz Shademan, Leila Sabour Takanlou, Maryam Sabour Takanlou, Alireza Nourazarian.
      Cancer therapy is on the brink of a significant transformation with the inclusion of patient-derived organoids (PDOs) in drug development. These three-dimensional cell cultures, directly derived from a patient's tumor, accurately replicate the complex structure and genetic makeup of the original cancer. This makes them a promising tool for advancing oncology. In this review, we explore the practical applications of PDOs in clinical drug screening and pharmacognostic assessment, as well as their role in refining therapeutic strategies. We provide insights into the latest advancements in PDO technology and its implications for predicting treatment responses and facilitating novel drug discoveries. Additionally, we address the operational challenges associated with incorporating PDOs into the drug development process, such as scaling up organoid cultures, ensuring consistent results, and addressing the ethical use of patient-derived materials. Aimed at researchers, clinicians, and key stakeholders in oncology, this article aims to succinctly present both the extraordinary potential and the obstacles to integrating PDOs, thereby shedding light on their prospective impact on the future of cancer treatment.
    Keywords:  cancer therapy; drug development; patient-derived organoids; personalized medicine; preclinical drug screening
    DOI:  https://doi.org/10.3389/fcell.2024.1401504
  13. Artif Cells Nanomed Biotechnol. 2024 Dec;52(1): 334-344
    Factors affecting response variables with emphasis on drug release and loading for optimization of liposomes.
    Shantanu Pande.
      Drug delivery through Liposomes has shown tremendous potential in terms of the therapeutic application of nanoparticles. There are several drug-loaded liposomal formulations approved for clinical use that help mitigate harmful effects of life-threatening diseases. Developments in the field of liposomal formulations and drug delivery have made it possible for clinicians and researchers to find therapeutic solutions for complicated medical conditions. A key aspect in the development of drug-loaded liposomes is a careful review of optimization techniques to improve the overall formulation stability and efficacy. Optimization studies help in improving/modulating the various properties of drug-loaded liposomes and are vital for the development of this class of delivery systems. A comprehensive overview of the various process variables and factors involved in the optimization of drug-loaded liposomes is presented in this review. The influence of different independent variables on drug release and loading properties with the application of a statistical experimental design is also explained in this article.
    Keywords:  Nanoparticles; drug loading; experimental design; liposomes; optimization
    DOI:  https://doi.org/10.1080/21691401.2024.2360634
  14. Cardiovasc Toxicol. 2024 Jun 07.
    Extracellular Vesicles in Cardiovascular Pathophysiology: Communications, Biomarkers, and Therapeutic Potential.
    Zhe Cui, Ling Zhang, Guangyu Hu, Fuyang Zhang.
      Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs.
    Keywords:  Cardiovascular Diseases; Extracellular vesicles; Heart; Pathophysiology
    DOI:  https://doi.org/10.1007/s12012-024-09875-0
  15. Front Immunol. 2024 ;15 1384946
    The involvement and application potential of exosomes in breast cancer immunotherapy.
    Yun Wang, Qiji Ma, Tielin Wang, Jie Xing, Qirong Li, Dongxu Wang, Gang Wang.
      Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.
    Keywords:  breast cancer; exosomes; immunity; tumor immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2024.1384946
  16. Cancer Lett. 2024 May 31. pii: S0304-3835(24)00383-5. [Epub ahead of print] 216989
    Exosome-based anticancer vaccines: From Bench to Bedside.
    Guo Zhao, Yuning Wang, Shujun Xing, Yale Jiang, Jiatong Ding, Yuanting Cai, Peiwen Ma, Huilei Miao, Yuan Fang, Ning Jiang, Dandan Cui, Yue Yu, Qiyu Tang, Shuhang Wang, Ning Li.
      Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction.
    Keywords:  Exosomes; cancer vaccines; clinical translation; immunotherapy; tumor immunity
    DOI:  https://doi.org/10.1016/j.canlet.2024.216989
  17. AAPS PharmSciTech. 2024 Jun 06. 25(5): 129
    Revolutionizing Lung Cancer Treatment: Innovative CRISPR-Cas9 Delivery Strategies.
    Dilpreet Singh.
      Lung carcinoma, including both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains a significant global health challenge due to its high morbidity and mortality rates. The objsective of this review is to meticulously examine the current advancements and strategies in the delivery of CRISPR-Cas9 gene-editing technology for the treatment of lung carcinoma. This technology heralds a new era in molecular biology, offering unprecedented precision in genomic modifications. However, its therapeutic potential is contingent upon the development of effective delivery mechanisms that ensure the efficient and specific transport of gene-editing tools to tumor cells. We explore a variety of delivery approaches, such as viral vectors, lipid-based nanoparticles, and physical methods, highlighting their respective advantages, limitations, and recent breakthroughs. This review also delves into the translational and clinical significance of these strategies, discussing preclinical and clinical studies that investigate the feasibility, efficacy, and safety of CRISPR-Cas9 delivery for lung carcinoma. By scrutinizing the landscape of ongoing clinical trials and offering translational perspectives, we aim to elucidate the current state and future directions of this rapidly evolving field. The review is structured to first introduce the problem and significance of lung carcinoma, followed by an overview of CRISPR-Cas9 technology, a detailed examination of delivery strategies, and an analysis of clinical applications and regulatory considerations. Our discussion concludes with future perspectives and challenges, such as optimizing delivery strategies, enhancing specificity, mitigating immunogenicity concerns, and addressing regulatory issues. This comprehensive overview seeks to provide insights into the potential of CRISPR-Cas9 as a revolutionary approach for targeted therapies and personalized medicine in lung carcinoma, emphasizing the importance of delivery strategy development in realizing the full potential of this groundbreaking technology.
    Keywords:  CRISPR-Cas9; clinical relevance; gene delivery; lung carcinoma; strategies; therapies
    DOI:  https://doi.org/10.1208/s12249-024-02834-6
  18. Artif Cells Nanomed Biotechnol. 2024 Dec;52(1): 355-369
    Role and therapeutic perspectives of extracellular vesicles derived from liver and adipose tissue in metabolic dysfunction-associated steatotic liver disease.
    Wandi Li, Lili Yu.
      The global epidemic of metabolic diseases has led to the emergence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which pose a significant threat to human health. Despite recent advances in research on the pathogenesis and treatment of MASLD/MASH, there is still a lack of more effective and targeted therapies. Extracellular vesicles (EVs) discovered in a wide range of tissues and body fluids encapsulate different activated biomolecules and mediate intercellular communication. Recent studies have shown that EVs derived from the liver and adipose tissue (AT) play vital roles in MASLD/MASH pathogenesis and therapeutics, depending on their sources and intervention types. Besides, adipose-derived stem cell (ADSC)-derived EVs appear to be more effective in mitigating MASLD/MASH. This review presents an overview of the definition, extraction strategies, and characterisation of EVs, with a particular focus on the biogenesis and release of exosomes. It also reviews the effects and potential molecular mechanisms of liver- and AT-derived EVs on MASLD/MASH, and emphasises the contribution and clinical therapeutic potential of ADSC-derived EVs. Furthermore, the future perspective of EV therapy in a clinical setting is discussed.
    Keywords:  Metabolic dysfunction-associated steatotic liver disease; adipose tissue; adipose-derived stem cell; extracellular vesicle; liver
    DOI:  https://doi.org/10.1080/21691401.2024.2360008
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