Exosome-Encased Nucleic Acid Scaffold Chemotherapeutic Agents for Superior Anti-Tumor and Anti-Angiogenesis Activity

外泌体包裹的核酸支架化疗剂具有优异的抗肿瘤和抗血管生成活性

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作者:Ryan P McNamara, Anthony B Eason, Yijun Zhou, Rachele Bigi, Jack D Griffith, Lindsey M Costantini, Michelle A Rudek, Nicole M Anders, Blossom A Damania, Dirk P Dittmer

Abstract

Extracellular vesicles (EVs), or exosomes, play a pivotal role in tumor growth and metastasis, such as in the case of Kaposi Sarcoma. By loading tumor-derived EVs with chemotherapeutic drugs, we noted that their pro-tumor/pro-angiogenic phenotype was converted into an anti-tumor phenotype in vivo. Drug concentration in EVs was significantly higher than in clinically approved liposome formulation, as retention was facilitated by the presence of miRNAs inside the natural EVs. This demonstrates a new mechanism by which to increase the payload capacity of nanoparticles. By exploiting the targeting preferences of tumor-derived EVs, chemotherapeutics can be directed to specifically poison the cells and the microenvironment that enables metastasis.

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