PGC1α expression using targeted redox-responsive nanogels protects against prostate cancer in vivo

We confirmed sustained PGC1α expression, and increased mitochondrial protein content, indicative of enhanced mitochondrial biogenesis. These nanogels, which were prepared in situ using a nanopolymerization technique, exhibited high mRNA loading capacity, low cytotoxicity, and redox-responsive cargo release, enabling controlled cytosolic delivery following intracellular glutathione-mediated degradation. In vivo, systemic administration of the PSMA-targeted NT-PGC1α mRNA-loaded nanogels resulted in tumour-preferential accumulation and significant suppression of xenograft growth (by 73.4% relative to untreated control), with minimal systemic toxicity.

This study presents the first example of a prostate-targeted, disulfide-crosslinked nanogel system for mRNA-mediated metabolic reprogramming in prostate cancer, and highlights its promise as a platform for future RNA-based targeted and precision stimuli-responsive cancer therapies.