Synergized Multimodal Therapy for Safe and Effective Reversal of Cancer Multidrug Resistance Based on Low-Level Photothermal and Photodynamic Effects.
Synergized Multimodal Therapy for Safe and Effective Reversal of Cancer Multidrug Resistance Based on Low-Level Photothermal and Photodynamic Effects.
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DOI:
10.1002/smll.201800785
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发表时间:
2018-06
期刊:
影响因子:
13.3
通讯作者:
Luming Xu;Jia Liu;Jiangbo Xi;Qilin Li;Bingcheng Chang;Xianming Duan;Guobin Wang;Shuai Wang;Zheng Wang;Lin Wang
中科院分区:
文献类型:
--
作者:
Luming Xu;Jia Liu;Jiangbo Xi;Qilin Li;Bingcheng Chang;Xianming Duan;Guobin Wang;Shuai Wang;Zheng Wang;Lin Wang
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.