Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy

被引：175

作者：

Chen, Fuming ^{[1
,2
]}

Zang, Zhongsheng ^{[3
]}

Chen, Ze ^{[1
]}

Cui, Liao ^{[2
]}

Chang, Zhiguang ^{[3
]}

Ma, Aiqing ^{[1
,2
]}

Yin, Ting ^{[1
]}

Liang, Ruijing ^{[1
]}

Han, Yutong ^{[1
,2
]}

Wu, Zhihao ^{[1
]}

Zheng, Mingbin ^{[1
,2
]}

Liu, Chenli ^{[3
]}

Cai, Lintao ^{[1
]}

机构：

[1] Chinese Acad Sci, CAS HK Joint Lab Biomat, CAS Key Lab Hlth Informat,Guangdong Key Lab Nanom, Shenzhen Engn Lab Nanomed & Nanoformulat,SIAT, Shenzhen 518055, Peoples R China

[2] Guangdong Med Univ, Key Lab Nanomed, Guangdong Key Lab Res & Dev Nat Drugs, Dongguan 523808, Peoples R China

[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Inst Synthet Biol, 1068 Xueyuan Ave, Shenzhen 518055, Peoples R China

来源：

BIOMATERIALS | 2019年 / 214卷

基金：

中国国家自然科学基金;

关键词：

Bacteria-driven nanophotosensitizer; Hypoxia-targeting; Tumor penetration; Mutual bioaccumulation; Photothermal therapy; DELIVERY-SYSTEM; GENE-EXPRESSION; TYPHIMURIUM; NANOPARTICLES; NANOLIPOSOMES; AREAS; MICE;

D O I：

10.1016/j.biomaterials.2019.119226

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Bacteria-driven drug-delivery systems have attracted great attention for their enhanced therapeutic specificity and efficacy in cancer treatment. YB1, a particularly attractive genetically modified safe Salmonella Typhimurium strain, is known to penetrate hypoxic tumor cores with its self-driven properties while remarkably avoiding damage to normal tissues. Herein, nanophotosensitizers (indocyanine green (ICG)-loaded nanoparticles, INPs) were covalently attached to the surface of YB1 with amide bonds to develop a biotic/abiotic cross-linked system (YB1-INPs) for tumor precision therapy. YB1 microswimmer retained its viability after efficiently linking with INPs. This YB1-INPs treatment strategy demonstrated specific hypoxia targeting to solid tumors, perfect photothermal conversion, and efficient fluorescence (FL) imaging properties. Benefited from the combined contribution of tumor tissue destruction and the bacteria-attracting nutrients generation after photothermal treatment, the bioaccumulation of YB1-INPs was significantly improved 14-fold compared to no photothermal intervention. Furthermore, YB1-INPs pervaded throughout the large solid tumor (>= 500 mm(3)). Under near-infrared (NIR) laser irradiation, YB1-INPs exhibited a dependable and highly efficient photothermal killing ability for eradicating the large solid tumor without relapse. This strategy of bacteria-driven hypoxia-targeting delivery has a great value for large solid tumors therapy with low toxicity and high efficiency.

引用

页数：11

共 47 条

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