Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications

Jiaqi Tian,1,* Zhengpu Han,1,2,* Dandan Song,1 Yanjie Peng,1 Min Xiong,3 Zhen Chen,2 Shuyin Duan,4 Lin Zhang1,5 1Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, People’s Republic of China; 2School of Public Health, Weifang Medical University, Weifang, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.com Shuyin Duan, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250001, People’s Republic of China, Tel +86-13419581411, Email shuyinduan@126.comAbstract: Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.Keywords: engineered exosomes, drug delivery, clinical application, preparation strateg