Journal
BIOMATERIALS
Volume 214, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119226
Keywords
Bacteria-driven nanophotosensitizer; Hypoxia-targeting; Tumor penetration; Mutual bioaccumulation; Photothermal therapy
Funding
- Key International S&T Cooperation Project [2015DFH50230]
- National Natural Science Foundation of China [31571013, 81701816, 81501591, 81671758, 21701033, 81501580, 91731302, 51502333]
- Natural Science Foundation of Guangdong Province [2017A030313079, 2017A030313726, 2016A030312006]
- Shenzhen Science and Technology Program [GJHS20140610152828690, JSGG20160331185422390, JCYJ2016042 9191503002, JCYJ20170818164139781]
- Shenzhen Peacock Team Project [KQTD2015033117210153]
- key research program of the Chinese Academy of Sciences [KFZD-SW-216]
- SIAT Innovation Program for Excellent Young Researchers [Y7G005]
- Dongguan Project on Social Science and Technology Development [2015108101019]
- LU JIAXI International team programme - K.C. Wong Education Foundation
- CAS [GJTD-2018-14]
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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.
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