Nanogels as innovative drug carriers for RNA-based skin cancer therapy: mechanistic insights and RNA encapsulation.

This review examines the potential application of nanogels as novel drug carriers for RNA-based therapy in the treatment of skin cancer. Relevant information was obtained from reputable scientific databases, including peer-reviewed articles. Nanogels, characterized by their nanoscale size and three-dimensional network structure, offer superior pharmacokinetic properties for drug delivery, including enhanced skin permeation, reduced burst release, and minimized systemic side effects. RNA molecules are very sensitive and can easily be degraded; therefore, by encapsulating them in nanogels, their stability, uptake, and delivery to skin cancer cells can be enhanced. This review elaborates on the molecular pathways MAPK/ERK/ PI3K/AKT/mTOR/p53/Hedgehog/NF-κB Pathways in skin cancers and the techniques for loading RNA into nanogels, such as electrostatic interactions, polymer-drug attachment, and LBL deposition. It also explains the mode of action of these nanogel-based drug delivery systems, which includes cellular uptake, intracellular targeting, RNA delivery, and gene silencing mechanisms. The issues of interest and concern in the context of large-scale production and clinical utilization of RNA-loaded nanogels are discussed. The current review addresses the existing gap by integrating pathway-level mechanistic insights in skin cancer with recent advances in nanogel-mediated RNA delivery, highlighting how these systems may overcome current limitations of conventional therapies and enable more precise and effective treatment strategies.