适配体功能化外泌体在肿瘤靶向治疗中的应用

The Application of Aptamer Functionalized Exosomes in Tumor-Targeted Therapy

传统的肿瘤治疗方法因缺乏足够的靶向性而会产生严重的毒副作用。外泌体(exosome)是一种天然的纳米囊泡,参与细胞间的信息传递,并且作为药物递送载体具有出色的性能优势,包括低免疫原性、低毒性和能够穿越天然屏障等特点。然而以外泌体为载体的药物递送系统的靶向能力仍有不足。适配体(aptamer)是一类化学合成的单链核酸分子,具有分子质量小、易于修饰和免疫原性低等特点,可作为亲和性配体与靶向分子特异性结合。通过在外泌体表面修饰适配体,药物可以被精确递送到肿瘤细胞发生部位,从而实现对肿瘤的靶向治疗,提高肿瘤治疗效果,减少毒副作用。本篇综述将重点讨论适配体功能化外泌体药物靶向递送系统在各种肿瘤治疗方面的应用,并对其未来的挑战和机遇进行阐述。

Traditional tumor treatment methods lack sufficient targeting and can cause serious side effects.Exosomes are natural nanovesicles that carries a variety of biomoleculars such as nucleic acids,proteins,metabolites,etc.They participate in intercellular communication and serve as drug delivery carriers with exceptional performance advantages,including low immunogenicity,low toxicity,and the ability to traverse natural barriers.However,targeting ability of exosome-based drug delivery systems is still insufficient.Aptamer is a class of chemically synthesized single-stranded nucleic acid molecules,which have the characteristics of small molecular weight,easy modification and low immunogenicity,and can be used as affinity ligands to specifically bind to targeted molecules.Aptamer-modified exosomes can precisely deliver drugs to the site where tumor cells occur,thereby achieving targeted treatment of tumors,enhancing the effectiveness of tumor therapy,and reducing adverse effects.Aptamers can modify exosomes in a variety of ways,mainly including receptor-ligand binding,hydrophobic interactions,DSPE-PEG2000-Mal conjugation,ester bonding,click chemistry,which lays a solid foundation for the development and application of aptamer functionalized exosome drug delivery systems.At present,the aptamer functionalized exosome drug delivery system still faces the following problems,such as the difficulty of aptamer screening,the low efficiency of exosome isolation and purification,and the lack of safety research on the use of aptamer-functionalized exosomes as drug-targeting delivery systems.As long as the above problems are solved,the role of aptamer functionalized exosomes in the treatment of tumors can be maximized.This review will focus on the application of aptamer functionalized exosome drug targeting delivery systems in various tumor treatments,and elaborate on their future challenges and opportunities.