title: Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy.
abstract: The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 Jiangsu, PR China; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060 Guangdong, PR China. Electronic address: peng.huang@szu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Wenpei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Zhantong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060 Guangdong, PR China; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, College Park, MD 20742, United States.
authors.forename: Junkai
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 Jiangsu, PR China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leapman
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 Jiangsu, PR China; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093 Jiangsu, PR China. Electronic address: cjr.luguangming@vip.163.com.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: shawn.chen@nih.gov.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D065546:Drug Liberation; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry; D000068936:Theranostic Nanomedicine
chemical_list: D001672:Biocompatible Materials; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: CuS; Enhanced chemotherapy; Mild hyperthermia; Periodic mesoporous organosilicas; Theranostics; Tri-stimuli-responsive