Optimal delivery strategies for nanoparticle-mediated mRNA delivery

Abstract

Messenger RNA (mRNA) has emerged as a new and efficient agent for the treatment of various diseases. The success of lipid nanoparticles-mRNA against the novel coronavirus (SARS-CoV-2) pneumonia epidemic has...

Effect of zwitterionic sulfobetaine incorporation on blood behaviours, phagocytosis, and in vivo biodistribution of pH-responsive micelles with positive charges

“…Positively charged polymers are well known for their electrostatic interactions with cells and proteins. 49 For instance, the effect of chitosan or its nanoparticles on blood behaviours is dependent on its molecular weight and degree of deacetylation (DDA), both of which contribute to the density of the positive charges, e.g., high-molecular-weight chitosan is widely used for hemostasis and wound dressing owing to it triggering the extrinsic coagulation pathway via the adsorption of fibrinogen, activation of platelets, and release of coagulation factors, 50 whereas low-molecular-weight chitosan has a low risk of hemolysis, a mild anticoagulation activity through blocking the intrinsic coagulation pathway, and no effect on platelet activation and aggregation. 51,52 Similarly, chitosan nanoparticles assembled from high DDA induced platelet aggregation, while the ones assembled from low DDA had no effect on platelets but prolonged the coagulation.…”

Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery

“…Through proper design of the characteristics of LBNPs, proteins with intrinsic targeting abilities can be specifically incorporated into the protein corona of LBNPs to direct LBNPs to targeted sites through protein‐receptor interactions, effectively functioning as an indirect active targeting strategy. [ 69b,89 ]…”

Development of polypeptide-based materials toward messenger RNA delivery

“…1 The use of COVID-19 mRNA vaccines has been evolving throughout the pandemic, which highlights the great potential of nucleic acid-based formulations and has caused a dramatic increase in financial support and capital investment in nucleic acid therapeutics. [11][12][13][14][15][16][17][18][19] However, the cellular uptake of exogenous mRNA faces significant challenges, including steric hindrance effect and the electrostatic repulsion between the cell membranes and nucleic acids. 20,21 The successful delivery of mRNA is hampered by its vulnerability to hydrolytic and enzymatic degradation by nucleases in the bloodstream, as well as systemic side effects arising from its lack of specificity (Fig.…”