Formulation screening for local delivery of mRNA and photosensitizer to treat superficial tumor

Localized delivery of mRNA-based therapies has shown promise in cancer treatment, but challenges such as drug leakage and systemic toxicity remain. This study aimed to develop a locally retained lipid nanoparticle (LNP) system for the co-delivery of mRNA and the photosensitizer indocyanine green (ICG) to treat superficial tumors. By systematically optimizing the lipid composition and mRNA-to-ICG ratio, we achieved high encapsulation efficiency and localized protein expression. The LNP system demonstrated robust transfection efficiency and photothermal effects, with minimal off-target distribution. In vivo studies revealed significant tumor growth inhibition, highlighting the potential of this approach for localized cancer therapy. This study provides a novel strategy for the co-delivery of mRNA and photosensitizers, offering a promising avenue for the treatment of superficial tumors with minimal systemic exposure.