Towards Targeted Delivery Systems: Ligand Conjugation Strategies for mRNA Nanoparticle Tumor Vaccines

Figure 1

Established strategies for the conjugation of ligands onto polymeric and liposomal nanoparticles. (a) (Top) PLGA (poly(lactic-co-glycolic acid)) nanoparticles formed by copolymer PLGA-PEG-COOH are stabilized with normal surfactant and subsequently reacted with ligands bearing compatible linking groups. (Bottom) PLGA nanoparticles are stabilized with amphiphilic surfactants containing functionalizable molecules. PLGA nanoparticles, susceptible to hydrolysis, are purified by centrifugation to reduce water exposure time. (b) DC-targeting antibodies bearing compatible cross-linkers (e.g., -SH) are reacted with preformed liposomes to form immunoliposomes, which are purified by dialysis. (c) Electrostatically neutral ligands (mannose) are covalently conjugated to cationic polymers and directly used to formulate targeted nanoparticles. (d) Postinsertion functionalization of liposomes/lipopolyplexes. Formulated liposomes/lipopolyplexes are heated with micelles bearing targeting ligands at 55°C for at least 15 mins. The resultant ligand conjugated liposomes/lipopolyplexes can be used without further purification.

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