Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective f...Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.展开更多
Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous pla...Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra enzyme.During the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2.Material,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser irradiation.The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation.Due to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic microenvironment.Moreover,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.展开更多
基金Acknowledgements This research was supported in part by the National Basic Research Program of China （973 Program, Nos. 2013CB733802 and 2010CB934602） the National Science Foundation of China （NSFC, Nos. 81101101, 81201086, 81201129, 81201190, 51273165, 51172005 and 81028009）+1 种基金 the Chinese Academy of Sciences Professorship for Senior International Scientists （No. 2011T2J06） and the Intramural Research Program （IRP） of the National Institute of Biomedical Imaging and Bioengineering （NIBIB）, National Institutes of Health （NIH）. R. X. is partially supported by the China Scholarship Council.
基金supported by grants from the National Natural Science Key Foundation of China(grant No.81530048)the National Natural Youth Fund(grant No.81902485).
文摘Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.
基金supported by the National Program on Key Basic Research Project(Grant No.2014CB744504,China)the National Natural Science Foundation of China(Grant No.81530054)+1 种基金Guangdong Science and Technology Department(Grant No.2016ZC0086,China)Guangdong Science and Technology Department(Grant No.2017ZC0099,China)
文摘Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra enzyme.During the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2.Material,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser irradiation.The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation.Due to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic microenvironment.Moreover,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.
