Work

NIR-II biomimetic nanoplatform optogenetic CD274 editing of HNSCC immunogenicity for enhanced photoimmunotherapy

Year: 2026

Type: article

Abstract: Although immunotherapy has achieved impressive breakthroughs in head and neck squamous cell carcinoma (HNSCC), it still encounters significant challenges such as the intrinsic low-immunogenicity microenvironment and limited T-cell infiltration. In this work, we aimed to edit CD274 gene of HNSCC cells by optogenetics with second near-infrared (NIR-II) light, thereby reducing the CD274 expression and improving the efficacy of photo-immunogenic therapy. Specifically, a biomimetic nanoplatform (ARPC) was established by using an α-LDLR (low density lipoprotein receptor antibody) engineered red blood cell membrane (RBCm) to deliver NIR-II photothermal polymers and CRISPR/Cas9 plasmids. After intravenous injection into HNSCC mice, ARPC can induce heat stress upon NIR-II laser irradiation at tumor sites, causing the upregulation of Hsp70 to trigger CRISPR/Cas9 for CD274 editing. Moreover, the mild photothermal therapeutic effect of ARPC simultaneously induced immunogenic cell death in tumor cells for enhancing CD8+ T cell infiltration and proliferation, and thereby leading to photoimmunotherapy. This study provides an NIR-II optogenetic CRISPR/Cas9 CD274 for editing reprogrammed photo-immunogenic therapy strategy, showing great clinical potential for overcoming the low immunogenicity of HNSCC.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2026.102803