Hybrid Cell Membrane-Conjugated Photosensitive Hydrogel as a Tumor Vaccine for Promoting Cancer Immunotherapy

Abstract

Preventive tumor vaccines exhibit substantial potential in averting tumorigenesis; nevertheless, their clinical efficacy remains constrained by challenges in eliciting potent and long-lasting immune activation, which ultimately leads to subpar overall therapeutic performance. In this study, we designed a biofilm-based hydrogel as a highly efficient single-dose prophylactic tumor vaccine. A hybrid biofilm (TMBM), which combines bacterial membrane (BM) and tumor cell membrane (TM), was modified with methacrylated hyaluronic acid-gelatin methacrylate (HAMA-GelMA ) to form a gel formulation (HG-TMBM hydrogel). This hydrogel can encapsulate ginsenoside Rg3 (Rg3) within its micropores and rapidly gelate in situ following subcutaneous injection. Upon single administration of the HG-TMBM hydrogel/Rg3 vaccine, both TMBM and Rg3 are sustainably released owing to the degradable nature of the HAMA-GelMA matrix. TMBM actively targets dendritic cells (DCs) and efficiently induces their maturation. Concurrently, Rg3 modulates the immune microenvironment and enhances antigen presentation efficiency, providing robust support for subsequent antigen cross-presentation. Ultimately, the vaccine successfully elicits potent and long-lasting T lymphocyte-mediated immune responses and exhibits significant preventive efficacy against colon tumors. The present work constructs a sustained-action system for tumor prophylaxis, offering an innovative approach for the creative development of single-administration preventive tumor vaccines.