title: Using hollow carbon nanospheres as a light-induced free radical generator to overcome chemotherapy resistance.
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.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences , Beijing China.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yin
authors.forename: Pengyang
authors.initials: P
authors.lastname: Wang
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Lu-Hua
authors.initials: LH
authors.lastname: Zhang
authors.forename: An-Hui
authors.initials: AH
authors.lastname: Lu
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
mesh_terms: D001692:Biological Transport; D002244:Carbon / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007259:Infrared Rays; D007834:Lasers; D061986:MCF-7 Cells; D054118:Nanospheres / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D017382:Reactive Oxygen Species; D002244:Carbon; D004317:Doxorubicin