Synthetic nanomaterials for spleen-specific mRNA delivery.

In recent years, mRNA vaccine has achieved increasing interest owing to its high potency, safety, ease of production, and low-cost manufacturing. Currently approved mRNA vaccines are administered intramuscularly to transfect local antigen-presenting cells (APCs) to initiate low to moderate immune responses. Spleen, the largest secondary lymphoid organ in the body which contains a large number of APCs close to B and T lymphocytes, could be the ideal site for effective initiation of an enhanced immune response. Here, we provide an overview of the recent advances in the development of synthetic materials for spleen-specific mRNA delivery, and lipid nanoparticle-based approaches will be highlighted. We further discuss the main challenges for spleen-specific mRNA delivery to provide a reference for the development of next-generation synthetic nanomaterials with optimal properties.

In Situ Reprogramming of Immune Cells Using Synthetic Nanomaterials.

In the past decade, adoptive cell therapy with chimeric antigen receptor-T (CAR-T) cells has revolutionized cancer treatment. However, the complexity and high costs involved in manufacturing current adoptive cell therapy greatly inhibit its widespread availability and access. To address this, in situ cell therapy, which directly reprograms immune cells inside the body, has recently been developed as a promising alternative. Here, an overview of the recent progress in the development of synthetic nanomaterials is provided to deliver plasmid DNA or mRNA for in situ reprogramming of T cells and macrophages, focusing especially on in situ CAR therapies. Also, the main challenges for in situ immune cell reprogramming are discussed and some approaches to overcome these barriers to fulfill the clinical applications are proposed.

Delivery of nucleic acids using nanomaterials.

The increasing number of approved nucleic acid therapeutics demonstrates the potential for the prevention and treatment of a broad spectrum of diseases. This trend underscores the significant impact and promise of nucleic acid-based treatments in the field of medicine. Nevertheless, employing nucleic acids as therapeutics is challenging due to their susceptibility to degradation by nucleases and their unfavorable physicochemical characteristics that hinder delivery into cells. Appropriate vectors play a pivotal role in improving nucleic acid stability and delivering nucleic acids into specific cells. The maturation of delivery systems has led to breakthroughs in the development of therapeutics based on nucleic acids such as DNA, siRNA, and mRNA. Non-viral vectors have gained prominence among the myriad of nanomaterials due to low immunogenicity, ease of manufacturing, and simplicity of cost-effective, large-scale production. Here, we provide an overview of the recent advancements in nanomaterials for nucleic acid delivery. Specifically, we give a detailed introduction to the characteristics of polymers, lipids, and polymer-lipid hybrids, and provide comprehensive descriptions of their applications in nucleic acid delivery. Also, biological barriers, administration routes, and strategies for organ-selective delivery of nucleic acids are discussed. In summary, this review offers insights into the rational design of next-generation delivery vectors for nucleic acid delivery.