Inosine-Based Supramolecular Hydrogel for Highly Efficient PD-L1 Blockade Therapy via Mediating CD8~+ T Cells

Jiajia Qi; Tingting Ding; Tiannan LiuXin XiaShihong WuJiang LiuQianming ChenDunfang ZhangHang Zhao

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Inosine-Based Supramolecular Hydrogel for Highly Efficient PD-L1 Blockade Therapy via Mediating CD8~+ T Cells

机译：Inosine-Based Supramolecular Hydrogel for Highly Efficient PD-L1 Blockade Therapy via Mediating CD8~+ T Cells

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Inosine is proven to promote the proliferation and function of CD8~+ cytotoxiclymphocytes (CD8~+ T) under glucose restriction and enhance the efficacy ofprogrammed cell death protein ligand-1 (PD-L1) blockade therapy. However,systemic administration of high frequencies and large doses of inosine andanti-PD-L1 antibody (aPDL1) is required, which inevitably reduces bioavailabilityand causes severe immunological side effects. Therefore, it is crucial to developa drug delivery system to achieve gradient release of inosine and aPDL1 forlocal immunotherapy. In this study, an inosine-based supramolecular hydrogel,inosine-phenylenediboronic-isoguanosine (IPBisoG), is successfully developedfollowing a simple one-pot procedure. Both in vitro and in vivo studies demonstratethat the biocompatible and biodegradable IPBisoG hydrogel displaysexcellent stability and self-healing properties. Furthermore, the IPBisoGhydrogel is shown to achieve the gradual and sequential release of inosine andaPDL1. Inosine, which enhances the proliferation and function of CD8~+ T cells,together with aPDL1, the blocker of the immunosuppressive pathway in tumormicroenvironment, can highly enhance the in vivo efficacy of PD-L1 blockadetherapy. The employment of IPBisoG hydrogel is also shown to trigger systemicimmune responses. These results demonstrate that IPBisoG hydrogel can be apromising platform for tumor-local immunotherapy in the future.

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《Advanced functional materials》 |2022年第33期|2204273.1-2204273.16|共16页
作者
Jiajia Qi; Tingting Ding; Tiannan LiuXin XiaShihong WuJiang LiuQianming ChenDunfang ZhangHang Zhao;
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State Key Laboratory of Oral DiseasesNational Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of OralCarcinogenesis and ManagementMed-X Center for MaterialsWest China Hospital of StomatologySichuan UniversityChe;

Department of BiotherapyState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu, Sichuan 610041, P. R. China;

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正文语种英语
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CD8~+ T cells; immunotherapy; inosine; programmed cell death protein ligand-1; supramolecular hydrogels;

Inosine-Based Supramolecular Hydrogel for Highly Efficient PD-L1 Blockade Therapy via Mediating CD8~+ T Cells

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