Optoregulated mRNA Delivery Controls Pleiotropic Immune Signaling for Tumor-Targeted Therapy.

ABSTRACT: Spatiotemporal control of protein expression remains a critical challenge in messenger RNA (mRNA) therapeutics, particularly for tumor-targeted therapy. Here, we introduce a Light-Induced Transfection System (LITS) leveraging photosensitizing polymers to deliver mRNA systemically and activate its translation via light-triggered endosomal escape. This system enables localized protein expression in any irradiated tissue, allowing for spatial control of therapeutic effects. Using interleukin-2 (IL-2) as a model, we demonstrate that LITS can trigger proinflammatory cytokine levels in irradiated tumors, while inducing tolerogenic IL-2 levels in nonirradiated healthy tissues. This modulation of IL-2's pleiotropic effects provides both potent antitumor activity and reduced toxicity. Furthermore,

SUBMITTER: Chen P 

PROVIDER: S-EPMC12535396 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature