As a promising modality for cancer therapy,photodynamic therapy(PDT)still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment.To ameliorate such a situation,we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hy-drophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin(BSA-MH1148)and multi-kinase inhibitor Sorafenib(SRF)as a novel tumor ox-ygen and immune microenvironment regulation drug.Benefiting from the accumulation of SRF in tu-mors,BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms:(ⅰ)SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory.(ⅱ)SRF increased the oxygen supply via inducing tumor vessel normalization.Meanwhile,the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows:(ⅰ)Enhanced immunogenic cell death(ICD)production amplified by BSA-MHI148@SRF induced reactive oxygen species(ROS)generation enhanced T cell infiltration and improve its tumor cell killing ability.(ⅱ)BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenviron-ment.Finally,the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles,which could be potential for clinical cancer therapy.

Zaigang Zhou;Jiashe Chen;Yu Liu;Chunjuan Zheng;Wenjuan Luo;Lele Chen;Shen Zhou;Zhiming Li;Jianliang Shen

State Key Laboratory of Ophthalmology,Optometry and Vision Science,School of Ophthalmology and Optometry,School of Biomedical Engineering,Wenzhou Medical University,Wenzhou 325027,China;Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou 325000,China;Department of the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;School&Hospital of Stomatology,Wenzhou Medical University,Wenzhou 325027,China;Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou 325000,China

药学学报（英文版）

[1]Zaigang Zhou;Jiashe Chen;Yu Liu;Chunjuan Zheng;Wenjuan Luo;Lele Chen;Shen Zhou;Zhiming Li;Jianliang Shen-.Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy)[J].药学学报（英文版）,2022(11):4204-4223

MHI148,MH1148,ygen,mors

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