An oxygen reservoir-irrigated photoimmunotherapy of malignant melanoma  

作　　者：Yao Huang Tingting Peng Yangyan Chen Fapeng Zhang Wanshan Hu XinYi Gao Hongyu Chen Ping Tang Chuanbin Wu Xin Pan 

机构地区：[1]School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [2]International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China,Jinan University,Guangzhou 511436,China [3]College of Pharmacy,Jinan University,Guangzhou 511436,China [4]Department of Biliary-Pancreatic Surgery,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China [5]School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [6]Shenzhen University General Hospital,Shenzhen 518055,China

出　　处：《Nano Research》2023年第2期2875-2884,共10页纳米研究（英文版）

基　　金：supported by the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002);the Key Areas Research and Development Program of Guangzhou(No.202007020006);the Fundamental Research Funds for the Central Universities(No.21620356);the Natural Science Foundation of Guangdong Province(No.2021A1515012525);the Science and Technology Foundation of Guangdong(No.2021A0505080011).

摘　　要：Tumor hypoxia is the pivotal factor limiting the therapeutic efficacy of photodynamic therapy(PDT),and can be partly improved by either the oxygen economizing or the oxygen supplementation strategies.Nevertheless,the current studies scarcely integrated the merits of both strategies and neglected the bottleneck of poor oxygen infiltration in deep tumors,resulting in PDT resistance.Herein,we developed an oxygen reservoir-irrigated PDT which integrates oxygen supply,oxygen economizing,and oxygen infiltration altogether.Specifically,mitochondria-targeted mesoporous prussian blue nanoparticles(Ce6@TPB)were fabricated to bridge the gap between oxygen economizing and oxygen supplementation by reducing oxygen output while increasing oxygen input.Hyaluronidase-loaded microneedles were further developed to pave the way for deep PDT with increased infusion of oxygen and photosensitizer by degrading dense extracellular matrix.The modulation of tumor oxygenation and permeability during PDT leads to the complete eradication of primary melanoma and strong immunogenic cell death.Its further combination with checkpoint-blockade inhibitor greatly suppressed the proliferation of distal tumors by reprogramming immune microenvironments,as evidenced by the depletion of M2 macrophage,increased infiltration of anti-tumor immune cells,and elevated excretion of immune cytokines.Therefore,such an oxygen reservoir-irrigated PDT potentiates powerful photoimmunotherapy and provides a favorable prospect for tumor treatment.

关 键 词：oxygen reservoir prussian blue nanoparticle hyaluronidase microneedle photodynamic therapy tumor microenvironment 

分 类 号：R739.5[医药卫生—肿瘤] R730.51[医药卫生—临床医学]