PEGylated graphene oxide-mediated stimulation of vascular endothelial cells and responsive release of PD-1/PD-L1 inhibitor for efficient chemo-immunotherapy against cancer (Open Access)--颗粒学报PARTICUOLOGY

Wang, Y., Li, F., Wang, S., Meng, J., Zhang, X., & Wei, W. (2024). PEGylated graphene oxide-mediated stimulation of vascular endothelial cells and responsive release of PD-1/PD-L1 inhibitor for efficient chemo-immunotherapy against cancer. Particuology, 91, 280-290. https://doi.org/10.1016/j.partic.2024.03.005

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

Yan Wang^{a b c}, Feng Li^{a b c}, Shuang Wang^{a b c}, Jiaqi Meng^{a b c}, Xiao Zhang^{a b c *}, Wei Wei^{a b c *}

a State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China
b Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing, 100190, China
c School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China

10.1016/j.partic.2024.03.005

Volume 91, August 2024, Pages 280-290

Received 6 March 2024, Revised 20 March 2024, Accepted 22 March 2024, Available online 1 April 2024, Version of Record 17 April 2024.

E-mail: zhangxiao@ipe.ac.cn; weiwei@ipe.ac.cn

Highlights

• We developed GPi to promote nanomedicine intratumoral accumulation and T cell infiltration by stimulating VECs.

• BMS-202 could be responsively released from GPi in tumor site to blockade PD-1/PD-L1 axis.

• The nanomedicine we used was clinical drug, thus conferring the favorable practical translational potential.

Abstract

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.

Graphical abstract

Keywords

PEGylated graphene oxide; Vascular endothelial cells; Immune checkpoint blockade; Immunogenic cell death; Chemo-immunotherapy

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