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响应性双靶点外泌体作为联合癌症免疫治疗的药物载体

Responsive Dual-Targeting Exosome as a Drug Carrier for Combination Cancer Immunotherapy.

作者信息

Fan Yuanyuan, Zhou Yingshun, Lu Meng, Si Haibin, Li Lu, Tang Bo

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China.

出版信息

Research (Wash D C). 2021 Aug 31;2021:9862876. doi: 10.34133/2021/9862876. eCollection 2021.

Abstract

Recently, combination immunotherapy, which incorporates the activation of the immune system and inhibition of immune escape, has been proved to be a new powerful strategy for more efficient tumor suppression compared to monotherapy. However, the major challenge is how to integrate multiple immune drugs together and efficiently convey these drugs to tumor sites. Although a variety of nanomaterials have been exploited as carriers for targeting tumor issues and the delivery of multiple drugs, their potential toxicity, immune rejection, and stability are still controversial for clinical application. Here, we proposed endogenic exosomes as drug carriers to deliver two antibodies acting as tumor-targeting molecules and block checkpoint inhibitors with specific response to the tumor microenvironment and costimulatory molecules for further improvement of therapeutic effect. The versatile exosomes exhibit excellent biocompatibility and provide a combination immunotherapy platform with synergistic advantages of activation of immune response and inhibition of immune escape.

摘要

最近,联合免疫疗法,即结合免疫系统激活和免疫逃逸抑制,已被证明是一种比单一疗法更有效的强大新策略,可更有效地抑制肿瘤。然而,主要挑战在于如何将多种免疫药物整合在一起,并有效地将这些药物输送到肿瘤部位。尽管已开发出多种纳米材料作为靶向肿瘤组织和递送多种药物的载体,但它们潜在的毒性、免疫排斥和稳定性在临床应用中仍存在争议。在此,我们提出以内源性外泌体作为药物载体,递送两种作为肿瘤靶向分子的抗体,并阻断对肿瘤微环境具有特异性反应的检查点抑制剂以及共刺激分子,以进一步提高治疗效果。多功能外泌体具有出色的生物相容性,并提供了一个联合免疫治疗平台,具有激活免疫反应和抑制免疫逃逸的协同优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69d6/8426567/e4d1e1e005bd/RESEARCH2021-9862876.sch.001.jpg

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