一种基于免疫原性激活和免疫抑制逆转的仿生纳米颗粒的新型免疫化学疗法。

A novel immunochemotherapy based on immunogenicity-activated and immunosuppression-reversed biomimetic nanoparticles.

作者信息

Zuo Huaqin, Tao Junxian, Wang Manli, Xie Xiaoyan, Sun Mei

机构信息

Department of Hematology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu 225001 P. R. China

Department of Endocrinology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu 225001 P. R. China.

出版信息

RSC Adv. 2022 Oct 3;12(43):28104-28112. doi: 10.1039/d2ra04326b. eCollection 2022 Sep 28.

Abstract

Studies show that infiltrated myeloid-derived suppressor cells (MDSCs) are vital in the immunosuppressive tumor microenvironment and account for lymphoma refractoriness and recurrence. Here, we developed a biomimetic nanoplatform (PM-PLGA-DOX/GEM) in which platelet membranes (PM) wrap PLGA nanoparticles co-loaded with doxorubicin (DOX) and gemcitabine (GEM). PM-PLGA-DOX/GEM would accumulate in tumor tissues because of the enhanced permeation and retention (EPR) effect and the tumor cell-induced platelet aggregation (TCIPA) effect. GEM could eliminate the MDSCs in tumor tissues, thereby reversing the immunosuppressive tumor microenvironment. Furthermore, DOX could invoke the immunogenic cell death (ICD) of lymphoma cells. Consequently, numerous T cells were recruited and activated to improve the therapeutic effects. This study will offer a potential platform for clinical treatment of lymphoma and other solid tumors.

摘要

研究表明,浸润的髓源性抑制细胞(MDSCs)在免疫抑制性肿瘤微环境中至关重要,是淋巴瘤难治性和复发的原因。在此,我们开发了一种仿生纳米平台(PM-PLGA-DOX/GEM),其中血小板膜(PM)包裹着共载有阿霉素(DOX)和吉西他滨(GEM)的聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒。由于增强的渗透和滞留(EPR)效应以及肿瘤细胞诱导的血小板聚集(TCIPA)效应,PM-PLGA-DOX/GEM会在肿瘤组织中积聚。GEM可以消除肿瘤组织中的MDSCs,从而逆转免疫抑制性肿瘤微环境。此外,DOX可以引发淋巴瘤细胞的免疫原性细胞死亡(ICD)。因此,大量T细胞被募集并激活,以提高治疗效果。本研究将为淋巴瘤和其他实体瘤的临床治疗提供一个潜在的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbf2/9527569/1867ae184d88/d2ra04326b-f1.jpg

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