Photothermal therapy(PTT)has been proposed as an advanced patient-centered strategy for tumor treatment.Nevertheless,the uncertain safety of conventional photothermal conversion agents and the presence of intracellula...Photothermal therapy(PTT)has been proposed as an advanced patient-centered strategy for tumor treatment.Nevertheless,the uncertain safety of conventional photothermal conversion agents and the presence of intracellular self-protective autophagy mechanisms pose obstacles to the clinical application and efficacy of PTT.As we are deeply aware of the seriousness of these problems,we herein proposed an efficacy-enhancing strategy based on an implantable membrane platform(PPG@PB-HCQ)constructed from poly(lactic acid)(PLA),poly(ɛ-caprolactone)(PCL)and gelatin(Gel)electrospun nanofibers(PPG)and loaded with the biodegradable high-efficiency photothermal conversion agent Prussian blue(PB)and the autophagy inhibitor hydroxychloroquine sulfate(HCQ).Cellular experiments confirmed that the PPG@PB-HCQ nanofiber membrane exhibited a significantly stronger tumor cell-killing effect compared with the PTT alone.This enhancement features by of blocking the fusion of autophagosomes with lysosomes.The intracellular overexpression of the proteins microtubule-associated protein 1 light chain 3(LC3)-II and p62 and the low expression of the proteins LC3-I and Rab7(members of the RAS oncogene family)further demonstrated autophagic flux blockade.Importantly,the potent antitumor effect of the PPG@PB-HCQ therapeutic platform in B16 tumor-bearing model mice verified the efficacy-enhancing strategy of synergistic PTT and protective autophagy blockade.The present study provides a promising strategy for solving the difficulties of tumor treatment,as well as a new perspective for designing novel treatment platforms.展开更多
基金supported by the Scientific Research Projects of Liaoning Provincial Department of Education(Grant No:LJKMZ20221354)Natural Science Foundation of Liaoning Province(Grant No:2023-MS-198)+2 种基金Cultivation Fund Project of National Natural Science Foundation(Grant No:PYJJ2021101)Career Development Support Program for Young and Middle-aged Teachers(Grant No:ZQN202208)of Shenyang Pharmaceutical UniversityThe authors would like to thank the Shiyanjia lab(www.Shiya njia.com)for the SEM,DSC and XRD tests.
文摘Photothermal therapy(PTT)has been proposed as an advanced patient-centered strategy for tumor treatment.Nevertheless,the uncertain safety of conventional photothermal conversion agents and the presence of intracellular self-protective autophagy mechanisms pose obstacles to the clinical application and efficacy of PTT.As we are deeply aware of the seriousness of these problems,we herein proposed an efficacy-enhancing strategy based on an implantable membrane platform(PPG@PB-HCQ)constructed from poly(lactic acid)(PLA),poly(ɛ-caprolactone)(PCL)and gelatin(Gel)electrospun nanofibers(PPG)and loaded with the biodegradable high-efficiency photothermal conversion agent Prussian blue(PB)and the autophagy inhibitor hydroxychloroquine sulfate(HCQ).Cellular experiments confirmed that the PPG@PB-HCQ nanofiber membrane exhibited a significantly stronger tumor cell-killing effect compared with the PTT alone.This enhancement features by of blocking the fusion of autophagosomes with lysosomes.The intracellular overexpression of the proteins microtubule-associated protein 1 light chain 3(LC3)-II and p62 and the low expression of the proteins LC3-I and Rab7(members of the RAS oncogene family)further demonstrated autophagic flux blockade.Importantly,the potent antitumor effect of the PPG@PB-HCQ therapeutic platform in B16 tumor-bearing model mice verified the efficacy-enhancing strategy of synergistic PTT and protective autophagy blockade.The present study provides a promising strategy for solving the difficulties of tumor treatment,as well as a new perspective for designing novel treatment platforms.
