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. 2024 Dec 13;137(24):2979–2995. doi: 10.1097/CM9.0000000000003455

Table 3.

Delivery strategies of mRNA vaccines.

Delivery strategies Structure Study findings References
Lipid-based
3-Comp Composed of nAcx-Cm lipids, permanent cationic lipids, and PEG lipids Better delivery efficiency and lung targeting than four- or five-component systems containing cholesterol and phospholipids, while still maintaining nanoparticle stability [77]
4N4T LNP (4-Comp) Composed of multicharged lipids with 4N4T, cholesterol, phospholipids, and PEG Providing enhanced mRNA delivery, robust immune responses, and improved safety compared to traditional LNP systems [78]
Inhalable LNP (5-Comp) Composed of ionizable lipids, helper lipids, phospholipids, and PEG The iLNP formulation is more suitable for inhalation and respiratory disease treatments because it can form effective and intact aerosolized particles. [79]
Polymer-based
F-PEI-based nanoparticle Composed of a F-PEI shell and an mRNA core Effective delivery of mRNA vaccines to exert anti-tumor effects without the need for adjuvants. [22]
PEG-Plys-based nanoparticles Composed of polyethylene glycol-polylysine (PEG-PLys) modified with triphenylphosphonium Significantly extended blood circulation time and increased mRNA distribution within solid tumors [83]
Anionic polymers nanoparticles Composed of a PLGA shell and an mRNA core Achieved a delivery efficiency of up to 80%, rapidly inducing protein translation [84]
VLP-based
Chimeric VLP Composed of antigen-encoding mRNA, unmethylated CpG oligonucleotides, and positively charged proteins within a phospholipid bilayer. Exerting adjuvant effects through structural modifications to elicit potent humoral and cellular immunity in prophylactic vaccines against HPV, cervical cancer, and breast cancer [8689]

CpG: Cytosine-phosphorothioate-guanine; F-PEI: Fluoroalkane-modified polyethylenimine; iLNP: Inhalable LNP; LNP: Lipid nanoparticle; mRNA: Messenger RNA; PEG: Polyethylene glycol; PEG-PLys: PEG-poly(l-lysine); PLGA: Poly(lactic-co-glycolic acid); VLP: Virus-like particle; 3-Comp: Three-component LNP; 4N4T: Four tertiary amine nitrogen atoms.