Application and problems in targeted delivery of antitumor drugs by exosomes derived from engineered mesenchymal stem cells
BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were"mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents"in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.
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