Journal of materials chemistry. BApr 13, 2026

Nanoparticles that respond to cell chemistry for improved mRNA delivery

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 14, 2026

Abstract

Redox-responsive nanoparticles may enhance mRNA delivery by improving cellular uptake and intracellular trafficking.

Redox-responsive nanoparticles disassemble in the reductive environment of the cytosol, aiding mRNA release.
Structure-function relationships link specific redox-labile chemistries to biological outcomes like endosomal escape and transfection efficiency.
Challenges such as tumor redox heterogeneity and preclinical evaluation limitations are identified as barriers to effective mRNA delivery.
Proposed strategies include developing multi-stimulus-responsive systems and improving manufacturing techniques to enhance delivery efficacy.

Simplified

The clinical success of mRNA vaccines during the COVID-19 pandemic highlighted the therapeutic potential of mRNA while exposing persistent delivery barriers, including intrinsic instability, poor cellular uptake, and inefficient intracellular trafficking. Redox-responsive nanoparticles (NPs) provide a promising strategy to improve mRNA delivery by undergoing stimulus-triggered disassembly in the reductive cytosol, facilitating efficient mRNA release, endosomal escape, and enhanced translation. This review elucidates emerging structure-function relationships by systematically linking redox-labile chemistries (, disulfide, diselenide, and polysulfide), carrier type, and NP architecture to key biological outcomes, including endosomal escape, redox responsiveness, transfection efficiency, and biodistribution. We further identify critical translational challenges-such as tumor redox heterogeneity, insufficient systematic preclinical evaluation, and manufacturing constraints-and propose actionable strategies, including multi-stimulus-responsive systems, microfluidic and process-analytical manufacturing, and formulation approaches to improve efficacy, reproducibility, and stability. Collectively, these insights provide a practical framework to guide the rational design and clinical translation of next-generation redox-responsive mRNA delivery platforms. e.g.

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Nanoparticles that respond to cell chemistry for improved mRNA delivery

Abstract

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