Dynamic Covalent Dextran Hydrogels as Injectable, Self-Adjuvating Peptide Vaccine Depots,ACS Chemical Biology

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Dynamic Covalent Dextran Hydrogels as Injectable, Self-Adjuvating Peptide Vaccine Depots
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2023-02-17 , DOI: 10.1021/acschembio.2c00938
Bowen Fan _{1,

2} , Diana Torres García ₃ , Marziye Salehi _{1,

3} , Matthew J Webber ₂ , Sander I van Kasteren ₃ , Rienk Eelkema ₁

Affiliation

Dextran-based hydrogels are promising therapeutic materials for drug delivery, tissue regeneration devices, and cell therapy vectors, due to their high biocompatibility, along with their ability to protect and release active therapeutic agents. This report describes the synthesis, characterization, and application of a new dynamic covalent dextran hydrogel as an injectable depot for peptide vaccines. Dynamic covalent crosslinks based on double Michael addition of thiols to alkynones impart the dextran hydrogel with shear-thinning and self-healing capabilities, enabling hydrogel injection. These injectable, non-toxic hydrogels show adjuvant potential and have predictable sub-millimolar loading and release of the peptide antigen SIINFEKL, which after its release is able to activate T-cells, demonstrating that the hydrogels deliver peptides without modifying their immunogenicity. This work demonstrates the potential of dynamic covalent dextran hydrogels as a sustained-release material for the delivery of peptide vaccines.

中文翻译：

动态共价葡聚糖水凝胶作为可注射、自我调节的肽疫苗库

基于葡聚糖的水凝胶由于其高生物相容性以及保护和释放活性治疗剂的能力，是用于药物输送、组织再生装置和细胞治疗载体的有前途的治疗材料。本报告描述了一种新型动态共价葡聚糖水凝胶的合成、表征和应用，作为肽疫苗的可注射储库。基于硫醇与炔酮的双迈克尔加成的动态共价交联赋予葡聚糖水凝胶剪切稀化和自愈能力，使水凝胶注射成为可能。这些可注射、无毒的水凝胶显示出佐剂潜力，并具有可预测的亚毫摩尔加载和肽抗原 SIINFEKL 释放，释放后能够激活 T 细胞，证明水凝胶在不改变其免疫原性的情况下输送肽。这项工作证明了动态共价葡聚糖水凝胶作为缓释材料用于输送肽疫苗的潜力。

更新日期：2023-02-17

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