mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond.

Adv Drug Deliv Rev

CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. Electronic address:

Published: March 2024

mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, the FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 and mRNA-1273) has further increased the interest and trust on this type of therapeutics. In order to achieve a significant therapeutic efficacy, the mRNA needs from a drug delivery system. In the last years, several delivery platforms have been explored, being the lipid nanoparticles (LNPs) the most well characterized and studied. A better understanding on how mRNA-based therapeutics operate (both the mRNA itself and the drug delivery system) will help to further improve their efficacy and safety. In this review, we will provide an overview of what mRNA cancer vaccines are and their mode of action and we will highlight the advantages and challenges of the different delivery platforms that are under investigation.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2024.115190DOI Listing

Publication Analysis

Top Keywords

lipid nanoparticles
8
mrna drug
8
drug delivery
8
delivery system
8
delivery platforms
8
mrna
4
mrna delivery
4
delivery systems
4
systems cancer
4
cancer immunotherapy
4

Similar Publications

Microfluidics Based Particle and Droplet Generation for Gene and Drug Delivery Approaches.

J Biomed Mater Res B Appl Biomater

February 2025

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir, Turkey.

Microfluidics-based droplets have emerged as a powerful technology for biomedical research, offering precise control over droplet size and structure, optimal mixing of solutions, and prevention of cross-contamination. It is a major branch of microfluidic technology with applications in diagnostic testing, imaging, separation, and gene amplification. This review discusses the different aspects of microfluidic devices, droplet generation techniques, droplet types, and the production of micro/nano particles, along with their advantages and limitations.

View Article and Find Full Text PDF

Solid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregnancy to vehicle mRNA to the placenta, data about the effect of premating exposure to SLNs on pregnancy outcome are scant. Considering that assumption of drug-delivering nanocarriers in reproductive age may potentially affect women's reproductive health, the aim of the present study was to evaluate whether repeated oral administration of SLNs to female mice prior to mating would influence key pregnancy outcomes.

View Article and Find Full Text PDF

Ganglioside-incorporating lipid nanoparticles as a polyethylene glycol-free mRNA delivery platform.

Biomater Sci

January 2025

Department of Bio and Brain Engineering, and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative.

View Article and Find Full Text PDF

Research progress of mosquito-borne virus mRNA vaccines.

Mol Ther Methods Clin Dev

March 2025

Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Diseases, Beijing, China.

In recent years, mRNA vaccines have emerged as a leading technology for preventing infectious diseases due to their rapid development and high immunogenicity. These vaccines encode viral antigens, which are translated into antigenic proteins within host cells, inducing both humoral and cellular immune responses. This review systematically examines the progress in mRNA vaccine research for major mosquito-borne viruses, including dengue virus, Zika virus, Japanese encephalitis virus, Chikungunya virus, yellow fever virus, Rift Valley fever virus, and Venezuelan equine encephalitis virus.

View Article and Find Full Text PDF

Atomic Insights into pH-Dependent and Water Permeation of mRNA-Lipid Nanoparticles.

Mol Pharm

January 2025

Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

The exposure of mRNA to water is likely to contribute to the instability of RNA vaccines upon storage under nonfrozen conditions. Using atomistic molecular dynamics (MD) simulations, we investigated the pH-dependent structural transition and water penetration behavior of mRNA-lipid nanoparticles (LNPs) with the compositions of Moderna and Pfizer vaccines against COVID-19 in an aqueous solution. It was revealed that the ionizable lipid (IL) membranes of LNPs were extremely sensitive to pH, and the increased acidity could cause a rapid membrane collapse and hydration swelling of LNP, confirming the high releasing efficiency of both LNP vaccines.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!