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

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外文摘要：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 immuno-genicity 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 upre-gulate 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.

外文关键词：

PEGylated graphene oxideVascular endothelial cellsImmune checkpoint blockadeImmunogenic cell deathChemo-immunotherapy

作者：

Yan Wang、Feng Li、Shuang Wang、Jiaqi Meng、Xiao Zhang、Wei Wei

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作者单位：

State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing,100190,China

Key Laboratory of Biopharmaceutical Preparation and Delivery,Chinese Academy of Sciences,Beijing,100190,China

School of Chemical Engineering,University of Chinese Academy of Sciences,Beijing,100049,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaBeijing Natural Science Foundation

项目编号：

2220835482372130JQ21027

出版年：

2024

DOI：

10.1016/j.partic.2024.03.005

颗粒学报(英文版)

中国颗粒学会　中国科学院过程工程研究所

颗粒学报(英文版)

CSTPCD

影响因子：0.632

ISSN：1674-2001

年,卷(期)：2024.91(8)