An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

被引：136

作者：

Cheng, Yuanyuan ^{[1
]}

Chen, Qian ^{[1
]}

Guo, Zhaoyang ^{[1
]}

Li, Mengwen ^{[1
]}

Yang, Xiaoying ^{[1
]}

Wan, Guoyun ^{[2
]}

Chen, Hongli ^{[2
]}

Zhang, Qiqing ^{[2
]}

Wang, Yinsong ^{[1
]}

机构：

[1] Tianjin Med Univ, Prov & Minist Cosponsored Collaborat Innovat Ctr, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China

[2] Xinxiang Med Univ, Sch Life Sci & Technol, Key Lab Biomed Mat, Xinxiang 453003, Henan, Peoples R China

来源：

ACS NANO | 2020年 / 14卷 / 11期

基金：

中国国家自然科学基金;

关键词：

dendritic large-pore mesoporous silica nanoparticles; stimulus response; homologous tumor targeting; holistic treatment; metastatic triple-negative breast cancer;

D O I：

10.1021/acsnano.0c05392

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Immunotherapy brings hope and opportunity to solve this challenge, while its clinical applications are greatly inhibited by the tumor immunosuppressive environment. Here, an intelligent biomimetic nanoplatform was designed based on dendritic large-pore mesoporous silica nanoparticles (DLMSNs) for suppressing metastatic TNBC by combining photothermal ablation and immune remodeling. Taking advantage of the ordered large-pore structure and easily chemically modified property of DLMSNs, the copper sulfide (CuS) nanoparticles with high photothermal conversion efficiency were in situ deposited inside the large pores of DLMSNs, and the immune adjuvant resiquimod (R848) was loaded controllably. A homogenous cancer cell membrane was coated on the surfaces of these DLMSNs, followed by conjugation with the anti-PD-1 peptide AUNP-12 through a polyethylene glycol linker with an acid-labile benzoic-imine bond. The thus-obtained AM@DLMSN@CuS/R848 was applied to holistically treat metastatic TNBC in vitro and in vivo. The data showed that AM@DLMSN@CuS/R848 had a high TNBC-targeting ability and induced efficient photothermal ablation on primary TNBC tumors under 980 nm laser irradiation. Tumor antigens thus generated and increasingly released R848 by response to the photothermal effect, combined with AUNP-12 detached from AM@DLMSN@CuS/R848 in the weakly acidic tumor microenvironment, synergistically exerted tumor vaccination, and T lymphocyte activation functions on immune remodeling to prevent TNBC recurrence and metastasis. Taken together, this study provides an intelligent biomimetic nanoplatform to enhance therapeutic outcomes in metastatic TNBC.

引用

页码：15161 / 15181

页数：21

共 51 条

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