Nature: Hydrogels for RNA delivery
Summary
RNA-based therapeutics have shown great promise for disease intervention at the genetic level, and some of these therapies have been approved for clinical use. The clinical success of RNA therapeutics largely depends on the use of chemical modification, ligand conjugation, or nonviral nanoparticles to enhance RNA stability and facilitate intracellular delivery. Unlike molecular-scale or nanoscale approaches, macroscopic hydrogels are soft, water-swellable three-dimensional structures with remarkable features such as biodegradability, tunable physicochemical properties, and injectability, and their application in RNA therapeutics has attracted great attention recently. Specifically, hydrogels can be designed to provide precise spatiotemporal control of the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This review provides a comprehensive overview of hydrogel-loaded and controlled-release hydrogel designs for RNA, highlights their biomedical applications, and provides our perspective on the opportunities and challenges of this exciting field of RNA delivery.
RNA-based therapeutics have shown great promise for disease intervention at the genetic level, and some of these therapies have been approved for clinical use. The clinical success of RNA therapeutics largely depends on the use of chemical modification, ligand conjugation, or nonviral nanoparticles to enhance RNA stability and facilitate intracellular delivery. Unlike molecular-scale or nanoscale approaches, macroscopic hydrogels are soft, water-swellable three-dimensional structures with remarkable features such as biodegradability, tunable physicochemical properties, and injectability, and their application in RNA therapeutics has attracted great attention recently. Specifically, hydrogels can be designed to provide precise spatiotemporal control of the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This review provides a comprehensive overview of hydrogel-loaded and controlled-release hydrogel designs for RNA, highlights their biomedical applications, and provides our perspective on the opportunities and challenges of this exciting field of RNA delivery.
RNA Loading in Hydrogels
Functional Hydrogels for RNA Loading and Delivery
Strategies for loading naked RNA into hydrogel networks
Functional characterization of hydrogels for controlled RNA delivery
Biomedical Applications of Hydrogel-Based RNA Delivery
Summarize
In this paper we discuss the use of hydrogels as RNA delivery systems from design to biomedical applications. The studies discussed in this article demonstrate that hydrogel systems not only enable sustained local delivery of RNA (avoiding repeated dosing), but also enable spatial and temporal control of the release rate. Further studies on the properties of RNA-loaded hydrogels, such as degradability, clearance, controlled release, and foreign body response, are urgently needed. Continued improvements in hydrogel design and fabrication are expected to bring these exciting materials closer to the clinical application of RNA therapeutics.
Highlights of this article
This is the first comprehensive review of the application and development of hydrogels in the field of RNA delivery, covering various types of RNA drugs (such as siRNA, miRNA, mRNA, etc.) and hydrogels (such as self-assembled hydrogels, chemically cross-linked hydrogels, biologically cross-linked hydrogels, etc.). Different methods of hydrogel loading RNA (such as physical adsorption, covalent coupling, nanocomposite, etc.) and different principles of hydrogel design (such as pH-sensitive, temperature-sensitive, light-sensitive, biological enzyme-sensitive, etc.) are introduced in detail, and their respective advantages, disadvantages and scope of application are analyzed. The biomedical applications of hydrogels in RNA delivery, such as anti-tumor, anti-inflammation, anti-infection, tissue regeneration, etc., were emphasized, and some typical cases and experimental results were shown. The opportunities and challenges faced by hydrogels in RNA delivery were proposed, such as increasing drug loading, optimizing release kinetics, enhancing targeting ability, reducing immune response, etc.
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