Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

被引：24

作者：

Liang, Kaifan ^{[1
,2
,3
]}

Sun, Yinzhe ^{[1
,2
,3
]}

Xie, Laozhi ^{[1
,2
,3
]}

Liu, Yipu ^{[1
,2
,3
]}

You, Yang ^{[1
,2
,3
]}

Xu, Jianpei ^{[1
,2
,3
]}

Ma, Fenfen ^{[1
,2
,3
]}

Huang, Yukun ^{[4
]}

Song, Qingxiang ^{[4
]}

Xiao, Wenze ^{[5
]}

Huang, Jianming ^{[6
]}

Gao, Xiaoling ^{[4
]}

Chen, Jun ^{[1
,2
,3
]}

机构：

[1] Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China

[2] Fudan Univ, Shanghai Pudong Hosp, Shanghai 201203, Peoples R China

[3] Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Univ Collaborat Innovat Ctr Translat Med, Dept Pharmacol & Chem Biol, State Key Lab Oncogenes & Related Genes,Sch Med, Shanghai 200025, Peoples R China

[5] Fudan Univ, Shanghai Pudong Hosp, Dept Rheumatol, Pudong Med Ctr, Shanghai 201399, Peoples R China

[6] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China

来源：

ACS NANO | 2024年 / 18卷 / 08期

基金：

中国国家自然科学基金;

关键词：

cancer nanovaccines; tumor-derived exosomes; 70 kDa heat shock proteins; cancer immunotherapy; HEAT-SHOCK PROTEINS; DENDRITIC CELLS; NANOPARTICLES; EXOSOMES; DELIVERY; VACCINES; IMPROVE;

D O I：

10.1021/acsnano.4c01050

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer alpha-mangostin (alpha M) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (alpha M-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, alpha M-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, alpha M-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

引用

页码：6702 / 6717

页数：16

共 61 条

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