期刊
SMALL
卷 14, 期 31, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201800785
关键词
drug delivery; drug resistance; gold-nanodot-decorated hollow carbon nanospheres; hyaluronic acid; multimodal therapy; weak photophysical and photochemical effects
类别
资金
- National Natural Science Foundation of China Programs [81402875, 81472740, 81572866, 81671904, 51173055]
- National Program on Key Basic Research Project (973 Program) [2013CBA01600]
- Hundreds of Talents Program of Hubei Province
- International Science and Technology Corporation Program of Chinese Ministry of Science and Technology [S2014ZR0340]
- Science and Technology Program of Chinese Ministry of Education [113044A]
- Frontier Exploration Program of Huazhong University of Science and Technology [2015TS153]
- Natural Science Foundation Program of Hubei Province [2015CFA049, 2016CFB263, 2017CFB652]
- Fundamental Research Funds for the Central Universities [2017KFYXJJ241]
- Research Fund of Public Welfare in Health Industry of the Health Ministry of China [201402015]
- Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST
Despite the therapeutic usefulness of near-infrared irradiation (NIR)-induced potent photothermal effects (PTE) and photodynamic effects (PDE), they inevitably damage normal tissues, often posing threat to life when treating tumors adjacent to key organs or major blood vessels. In this study, the frequently overlooked, weak PTE and PDE (no killing capability) are employed to synergize chemotherapy against multidrug resistance (MDR) without impairing normal tissues. An NIR-responsive nanosystem, gold (Au)-nanodot-decorated hollow carbon nanospheres coated with hyaluronic acid, is synthesized as a doxorubicin (DOX) carrier with excellent photothermal and photodynamic properties. Upon low-level infrared irradiation, the mild heat of weak PTE moderately boosts DOX unloading, meanwhile the weak PDE moderately disturbs the P-glycoprotein function for retaining intracellular DOX by impairing mitochondrial ATP production. These two moderate alterations are quantitatively and functionally sufficient to augment the efficacy of chemotherapy in reversing MDR without damaging neighboring tissue. Thus, this work creates a gold-dot-decorated nanocarbon spheres based nanosystem for trimodal therapy, reveals the therapeutic value of the frequently ignored weak PTE/PDE, and demonstrates that synergizing with chemotherapy to overcome drug resistance does not necessarily require potent PTE/PDE.
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