Journal
ACS NANO
Volume 11, Issue 10, Pages 10159-10174Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b04737
Keywords
nanoparticles; hypoxia; radiotherapy; radiosensitization; photothermal therapy; tungsten
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Funding
- National Key'R&D Program of China [2017YFA0205400]
- National Natural Science Foundation of China [21474047, 81671751, 81371516, 81502608]
- Technique Development Foundation of Nanjing (Outstanding Youth Foundation) [JQX15004]
- Industry-University-Research Collaboration project of Jiangsu Province [BY2015041-01]
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Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm-featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment-targeting NPs (similar to 6 mm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced 'computed tomography (CT) with higher spatial resolution. Once irradiated with,a 1064,nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia-induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment hypoxic tumor management.
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