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Immunostimulant nanomodulator boosts antitumor immune response in triple negative breast cancer by synergism of vessel normalization and photothermal therapy

查看全文 作　　者：Hao [1]Jiang;Yilang [2]He;Jia [3]Zhao;Ruimin [4]Chang;Hailun [2]He;Tan [2]Li;Xingyu [2]Zhang;Bo [5]Shu;Wenxuan [6]Zhang;Huaiyu [7]Wang;Jing [2]Liu;Shubing [3]Zhang;Yuetao [2]Zhao 高影响力作者 机构地区：[1]Department of Biomedical Informatics,School of Life Sciences,Central South University,Changsha 410013,China;[2]Department of Biochemistry and Molecular Biology,Hunan Province Key Laboratory of Basic and Applied Hematology,School of Life Sciences,Central South University,Changsha 410013,China;[3]Department of Cell Biology,School of Life Sciences,Central South University,Changsha 410013,China;[4]The Department of Dermatology,Xiangya Clinical Research Center for Cancer Immunotherapy,Hunan Key Laboratory of Skin Cancer and Psoriasis,Hunan Engineering Research Center of Skin Health and Disease,Xiangya Hospital,Central South University,No.87 Xiangya Road,Changsha 410008,China;[5]Department of General Surgery,The Second Xiangya Hospital,Central South University,Changsha 410011,China;[6]State Key Laboratory of Natural and Biomimetic Drugs,Department of Chemical Biology,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China;[7]Institute of Biomedicine and Biotechnology,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China高影响力机构 出　　处：《Nano Research》索引2023年第16卷第8期,共15页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation of China(Nos.32000931,81672632,81972312,and 82103184);the Natural Science Foundation of Hunan Province for outstanding Young Scholars(No.2021JJ20083);Natural Science Foundation of Hunan Province of China(Nos.2021JJ30912,2021JJ40720 and 2021JJ30950);the science and technology innovation Program of Hunan Province(No.2022RC1165);the Open Sharing Fund for the Largescale Instruments and Equipment of Central South University,Changsha,China. 摘　　要：Tumor vascular dysfunction and immune suppression predict poor outcomes of tumor therapy.Combination of photothermal therapy(PTT)and vessel normalization with tumor immunotherapy is promising to augment antitumor benefit.Herein,we develop a potential immunostimulatory nanomodulator for treatment of triple-negative breast cancer(TNBC)treatment via synergism of PTT,vessel normalization,and priming of tumoral suppressive immune microenvironment by blocking transforming growth factor-β(TGF-β)pathway.The nanomodulator,namely Vac@Apt@BPs,is developed by conjugation of TGF-βinhibitor Vactosertib(Vac)and nucleolin-recognizing aptamer(Apt)on the surface of black phosphorus nanoparticles(BPs).Vac@Apt@BPs show good accumulation in TNBC via aptamer-induced active targeting of TNBC.Via the blockade of TGF-βsignaling,Vac@Apt@BPs effectively inhibit the formation of tumor neovascular,and normalize the vessels to recover vascular integrity and alleviate the hypoxia stress.Together with the tumor eradication and immunogenic cell death via PTT,robust immune response was boosted by promoted maturation of dendritic cells,suppression of regulatory T cells,and stimulation of effective T cells.This synergistic therapeutic strategy potentially suppresses the growth of TNBC in mice. 关 键 词：vessel normalization photothermal therapy black phosphorus triple negative breast cancer transforming growth factor-β
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