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Using Hollow Carbon Nanospheres as a Light-Induced Free Radical Generator To Overcome Chemotherapy Resistance

Journal of the American Chemical Society2015Vol. 137(5), pp. 1947–1955

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Liming Wang, Qiang Sun, Xin Wang, Tao Wen, Jun‐Jie Yin, Pengyang Wang, Ru Bai, Xiang‐Qian Zhang, Luhua Zhang, An‐Hui Lu, Chunying Chen

Abstract

Under evolutionary pressure from chemotherapy, cancer cells develop resistance characteristics such as a low redox state, which eventually leads to treatment failures. An attractive option for combatting resistance is producing a high concentration of produced free radicals in situ. Here, we report the production and use of dispersible hollow carbon nanospheres (HCSs) as a novel platform for delivering the drug doxorubicine (DOX) and generating additional cellular reactive oxygen species using near-infrared laser irradiation. These irradiated HCSs catalyzed sufficiently persistent free radicals to produce a large number of heat shock factor-1 protein homotrimers, thereby suppressing the activation and function of resistance-related genes. Laser irradiation also promoted the release of DOX from lysosomal DOX@HCSs into the cytoplasm so that it could enter cell nuclei. As a result, DOX@HCSs reduced the resistance of human breast cancer cells (MCF-7/ADR) to DOX through the synergy among photothermal effects, increased generation of free radicals, and chemotherapy with the aid of laser irradiation. HCSs can provide a unique and versatile platform for combatting chemotherapy-resistant cancer cells. These findings provide new clinical strategies and insights for the treatment of resistant cancers.

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Abstract

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