PEGylated graphene oxide-mediated stimulation of vascular endothelial cells and responsive release of PD-1/PD-L1 inhibitor for efficient chemo-immunotherapy against cancer Author links open overlay panel  

作　　者：Yan Wang Feng Li Shuang Wang Jiaqi Meng Xiao Zhang Wei Wei 

机构地区：[1]State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing,100190,China [2]Key Laboratory of Biopharmaceutical Preparation and Delivery,Chinese Academy of Sciences,Beijing,100190,China [3]School of Chemical Engineering,University of Chinese Academy of Sciences,Beijing,100049,China

出　　处：《Particuology》2024年第8期280-290,共11页颗粒学报（英文版）

摘　　要：Immune checkpoint blockade(ICB)has emerged as a promising immunotherapeutic modality against cancer in the clinic.However,only 10-30%of patients respond to ICB,primarily due to poor immunogenicity and insufficient T cell infiltration in solid tumors.Herein,we presented an approach for high-performance cancer treatment using the programmed cell death protein-1 and programmed cell death ligand-1(PD-1/PD-L1)inhibitor(BMS-202)-loaded PEGylated graphene oxide(GPi).On the one hand,GPi dissociated tight junctions of vascular endothelial cells(VECs)in tumor,thus promoting the extravasation and intratumoral accumulation of liposomal doxorubicin(LipDox),which then effectively induced immunogenic cell death of tumor cells.On the other hand,GPi also stimulated VECs to upregulate the expression of cell-cell interaction molecules,such as intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1,which facilitated the infiltration of T cells in tumor.Beyond acting as a stimulator of VECs,GPi could exert responsive release of BMS-202 under the acidic tumor microenvironment and blockade PD-1/PD-L1 axis in tumors.Finally,the alternating administration of GPi and LipDox effectively inhibited tumor growth in a 4T1 tumor model,providing a novel treatment mode for chemo-immunotherapy.

关 键 词：PEGylated graphene oxide Vascular endothelial cells Immune checkpoint blockade Immunogenic cell death CHEMO-IMMUNOTHERAPY 

分 类 号：R730.5[医药卫生—肿瘤]