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化学进展 2021, Vol. 33 Issue (10): 1823-1840 DOI: 10.7536/PC201019 前一篇   后一篇

• 综述 •

细胞膜修饰的纳米载体与肿瘤免疫治疗

官启潇, 郭和泽, 窦红静*   

  1. 上海交通大学材料科学与工程学院 金属基复合材料国家重点实验室 上海 200240
  • 收稿日期:2020-02-16 修回日期:2020-05-28 出版日期:2021-10-20 发布日期:2021-03-04

Nanocarriers Modified by Cell Membrane and Their Applications in Tumor Immunotherapy

Qixiao Guan, Heze Guo, Hongjing Dou*   

  1. State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University,Shanghai 200240, China
  • Received:2020-02-16 Revised:2020-05-28 Online:2021-10-20 Published:2021-03-04

纳米载体由于其纳米尺度带来的独特生物功能性,可通过特定设计在生物体内靶向递送各类抗肿瘤药物,具有广泛而重要的应用前景。自肿瘤免疫疗法问世之后,各类纳米载体与肿瘤免疫治疗相结合,逐渐成为提升肿瘤免疫治疗效果的重要手段之一。其中,细胞膜修饰的纳米载体作为一类新型仿生药物载体平台,可使纳米载体获得天然细胞膜的伪装修饰,将细胞膜的特定功能与生物特性转移至纳米载体,使其具有更强的抗免疫清除、血液长循环和肿瘤靶向等特性,同时降低纳米递送系统的免疫原性和细胞毒性,在生物医学应用领域尤其是肿瘤免疫治疗中可发挥更大的作用。本文通过结合免疫治疗的机理,对近年来各种细胞膜修饰纳米载体系统的制备方法、作用机制以及在肿瘤免疫治疗中的应用研究进行综述,并在此基础上对未来的相关探索做出了展望。

Due to the unique biological functionality resulting from the nano scale, nanocarriers can deliver various kinds of anti-tumor drugs in vivo through specific design, showing an important application prospect. Since the advent of tumor immunotherapy, a brand-new anti-tumor method, the combination of various nanocarriers and tumor immunotherapy has gradually become one of the important means to improve the effect of tumor immunotherapy. Among them, as a new kind of biomimetic drug carrier platform, the nanocarrier modified by cell membrane can make the nanocarrier achieve the camouflage modification of natural cell membrane. Meanwhile, such a decoration is able to transfer the specific functions and biological characteristics of cell membrane to the nanocarrier, so that it is equipped with stronger ability of anti-immune clearance, long blood circulation and tumor targeting, and thus reduces the immunogenicity and cytotoxicity of nano delivery system. Therefore, the membrane modified nanocarriers can play a greater role in biomedical applications, especially in tumor immunotherapy. In this article, combined with the mechanism of immunotherapy, the preparation methods, anti-tumor mechanism and application research in tumor immunotherapy of nanocarrier systems modified by numerous kinds of cell membrane in recent years are reviewed, and on this basis, the related exploration in the future is prospected.

Contents

1 Introduction

2 Nanocarriers and tumor immunotherapy

3 Nanocarriers modified by cell membrane and their functionary mechanism

4 Application of cell membrane modified nanocarriers in tumor immunotherapy

4.1 Erythrocyte membrane modified nanocarriers

4.2 Platelet membrane modified nanocarriers

4.3 Immune cell membrane modified nanocarriers

4.4 Tumor cell membrane modified nanocarriers

4.5 Bacterial membrane modified nanocarriers

4.6 Other cell membrane modified nanocarriers

5 Conclusion and outlook

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图1 Man-RBC膜包覆的PLGA-SS-hgp100纳米颗粒(Man-RBC-NPhgp)的制备及其诱导抗肿瘤免疫的示意图[28]
Fig. 1 Schematic illustration of the preparation of Man-RBC membrane-coated PLGA-SS-hgp100 nanoparticles(Man-RBC-NPhgp) and induction of antitumor immunity[28]. Copyright 2015, American Chemical Society
图2 载有可选择性消除CTCs的Carfilzomib的NM-NPs颗粒(NM-NP-CFZ) 的制备及其定植位点示意图[42]
Fig. 2 Schematic illustration of NM-NPs loaded with Carfilzomib(NM-NP-CFZ) that selectively deplete CTCs and their site of colonization[42]. Copyright 2017, American Chemical Society
图3 (a) 癌细胞质膜部分包覆的PLGA 纳米颗粒(CCMF-PLGA NPs)的制备示意图;(b) 目的是确定这些伪装成癌细胞的纳米颗粒破坏癌细胞与基质细胞相互作用、减少转移并启动免疫系统以进行癌症免疫治疗的能力[64]
Fig. 3 (a) Schematic illustration of the preparation of cancer cell plasma membrane fraction-coated PLGA NPs(CCMF-PLGA NPs);(b) The purpose was to determine the ability of these cancer cell-mimicking NPs to disrupt cancer cell-stromal cell interactions, reduce metastasis, and prime the immune system for cancer immunotherapy[64]. Copyright 2019, American Chemical Society
图4 CMSN-GOx诱导的抗肿瘤免疫应答和增强抗PD-1免疫治疗示意图[78]
Fig. 4 Schematic illustration of antitumor immune response and enhanced anti-PD-1 immunotherapy induced by CMSN-GOx[78]. Copyright 2019, American Chemical Society
图5 细菌膜包被纳米颗粒(BNP)联合放射治疗(RT)诱导原位疫苗的效果示意图。(A)BNP如何与TME相互作用以增强APC摄取和激活的示意图。(B)BNP联合RT诱导原位疫苗的示意图。(C)BNP的组成及各组分的作用[89]
Fig. 5 Schematic diagram of the in situ vaccine effect elicited by combined RT and BNP. (A) A schematic of how a BNP interacts with the TME to enhance APC uptake and activation. (B) Schematic diagram of the in situ vaccine effect elicited by combined RT and BNP. (C) Composition of the BNP and the function of each BNP component.[89]. Copyright 2019, John Wiley and Sons
图6 MOF@FM用于肿瘤预防的示意图。(a) MOF@FM的制备;(b)接种MOF@FM疫苗预防肿瘤;(c) MOF@FM诱导免疫反应的机制[101]
Fig. 6 Schematic illustration of MOF@FM for tumor prevention.(a) Preparation of MOF@FM; (b) Vaccination of MOF@FM for tumor prevention;(c) Mechanisms of MOF@FM inducing immune responses[101]. Copyright 2019, Springer Nature
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