Redox-responsive nanoparticles for enhanced mRNA delivery: a comprehensive review

Area of Science:

• Biotechnology
• Materials Science
• Nanomedicine

Background:

• Messenger RNA (mRNA) therapeutics show great promise but face delivery challenges like instability and poor cellular uptake.
• Redox-responsive nanoparticles (NPs) offer a solution by degrading in the reducing cellular environment, aiding mRNA release and function.

Purpose of the Study:

• To review structure-function relationships in redox-responsive NPs for mRNA delivery.
• To identify challenges and propose strategies for clinical translation of these advanced delivery systems.

Main Methods:

• Systematic review linking redox-labile chemistries, NP types, and NP architecture to biological outcomes.
• Analysis of translational challenges and potential solutions for mRNA delivery.

Main Results:

• Established structure-function relationships for redox-responsive NPs, impacting endosomal escape, transfection efficiency, and biodistribution.
• Identified key challenges including tumor redox heterogeneity and manufacturing constraints.

Conclusions:

• Rational design of next-generation redox-responsive mRNA delivery platforms requires understanding the interplay between chemistry, architecture, and biological response.
• Proposed strategies like multi-stimulus responsiveness and advanced manufacturing can enhance efficacy and clinical translation.