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Journal of Controlled Release

Journal of Controlled Release

IF: 10.5
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In situ self-reassembling nanosystem enhances PD-L1 blockade for cancer immunotherapy

Published:4 December 2024 DOI: 10.1016/j.jconrel.2024.11.075
Chenglin Liang, Xinyi Ding, Xinni Li, Xiaojuan Jiang, Heng Yang, Hanxiao Yang, Kaikai Liu, Lin Hou

Abstract

Although immune checkpoint inhibitors (ICIs) have made great progress in cancer treatment, their off-tumor distribution, low affinity of traditional ICIs and insufficient T cells infiltration at tumor site limit immunotherapeutic efficacy. Herein, we engineer a highly specific and effective PD-L1 inhibitor (PEC) that modulates the level of binding sites with PD-L1. Specifically, PEC is a hybrid system composed of E. coli membrane expressing PD-L1 binding protein and cancer cell membrane. Notably, PEC can target the tumor site, produce oxygen in response to H2O2, rupture into membrane fragments, and reassemble to form vesicles retaining the PD-L1 binding protein. Through in situ fracture and reassembly, PEC transforms from a hybrid membrane to a single E. coli membrane, leading to the increased density of PD-L1 binding protein. Consequently, the reassembled vesicles can bind to more PD-L1 on tumor cells and induce its degradation in lysosomes. Furthermore, the cGAS-STING signaling activators HZD is encapsulated into PEC to promote T cells infiltration. We demonstrate that PEC@HZD achieves sequential T cells recruitment and functional enhancement, thus stimulating a powerful antitumor immune response. This work provides a new perspective on tailoring ICIs to improve cancer immunotherapy.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Triton X-100 9002-93-1 (C2H4O)nC14H22O 528 suppliers $18.00-$610.00
Phenylmethylsulfonyl fluoride 329-98-6 C7H7FO2S 400 suppliers $5.00-$2530.00
Deoxyribonuclease 9003-98-9 NULL 287 suppliers $58.00-$2170.00
DAPI 47165-04-8 C16H15N5 13 suppliers $504.53-$504.53

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