Inosine‐Based Supramolecular Hydrogel for Highly Efficient PD‐L1 Blockade Therapy via Mediating CD8+ T Cells. (25th May 2022)

• Record Type: Journal Article
• Authors: Qi, Jiajia; Ding, Tingting; Liu, Tiannan; Xia, Xin; Wu, Shihong; Liu, Jiang; Chen, Qianming; Zhang, Dunfang; Zhao, Hang
• Is Part Of: Advanced functional materials. Volume 32:Number 33(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-25
• Subjects: CD8 + T cells -- immunotherapy -- inosine -- programmed cell death protein ligand‐1 -- supramolecular hydrogels; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202204273
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Inosine is proven to promote the proliferation and function of CD8 + cytotoxic lymphocytes (CD8 + T) under glucose restriction and enhance the efficacy of programmed cell death protein ligand‐1 (PD‐L1) blockade therapy. However, systemic administration of high frequencies and large doses of inosine and anti‐PD‐L1 antibody (aPDL1) is required, which inevitably reduces bioavailability and causes severe immunological side effects. Therefore, it is crucial to develop a drug delivery system to achieve gradient release of inosine and aPDL1 for local immunotherapy. In this study, an inosine‐based supramolecular hydrogel, inosine‐phenylenediboronic‐isoguanosine (IPBisoG), is successfully developed following a simple one‐pot procedure. Both in vitro and in vivo studies demonstrate that the biocompatible and biodegradable IPBisoG hydrogel displays excellent stability and self‐healing properties. Furthermore, the IPBisoG hydrogel is shown to achieve the gradual and sequential release of inosine and aPDL1. Inosine, which enhances the proliferation and function of CD8 + T cells, together with aPDL1, the blocker of the immunosuppressive pathway in tumor microenvironment, can highly enhance the in vivo efficacy of PD‐L1 blockade therapy. The employment of IPBisoG hydrogel is also shown to trigger systemic immune responses. These results demonstrate that IPBisoG hydrogel can be a promising platform for tumor‐local immunotherapy in the future. Abstract : An inosine‐based supramolecular hydrogel is developed by introducing reversible borate ester linkages. The biocompatible and biodegradable hydrogel, which remarkably enhances tumoral drug retention, can serve as a reservoir for gradual and sequential release of inosine and anti‐programmed cell death protein ligand‐1 (PD‐L1) antibody and enhance PD‐L1 blockade therapy via supporting the proliferation and function of CD8 + T cells.