Covalent Conjugation of Polyethylenimine to Mesoporous Silica Nanoparticles for Therapeutic Agents Delivery

ABSTRACT

Mesoporous silica nanoparticles (MSNPs) have great potential for delivering both small‐molecule drugs and large therapeutic agents. PEI (polyethylenimine) coating enhances the drug delivery efficiency, stability, and functionalization capacity of MSNPs. However, coating MSNPs with PEI is generally performed in DMF, a solvent that is highly detrimental to therapeutic agents, including biologics and pharmaceuticals. Consequently, PEI coating after mRNA loading is most often achieved through physical adsorption, or alternatively, mRNA is attached to the surface of nanoparticles (NPs) following covalent PEI coating. In this study, we investigated the covalent attachment of PEI to MSNPs using solvents and conditions that are more compatible with sensitive molecules, such as DNA and RNA. This approach enabled the covalent attachment of PEI to MSNPs loaded with sensitive molecules. The results obtained with alternative solvents were compared with those obtained with DMF as a reference solvent. Our findings demonstrated that covalent PEI attachment in a chloroform:MeCN (20:80) mixture was more efficient than in DMF. Subsequently, mRNA‐loaded MSNPs were covalently coated with PEI using this solvent mixture, and the protective effect of the PEI coating on the loaded mRNA was evaluated. The PEI‐coated MSNPs offered enhanced protection for mRNA against RNase A compared to uncoated MSNPs.