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January 22nd, 2025

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Indian Institute of Science

biophysics

biorxiv

siRNA complexation with Galactose-Functionalized Dendrimer: PAMAM vs PETIM

Maity, T.Open in Google Scholar•Kumar, Y.Open in Google Scholar•Maiti, P. K.Open in Google Scholar

siRNA-based therapies hold promise for treating various diseases, but efficient and targeted delivery remains challenging. This study explored the potential of galactose-functionalized poly(amidoamine) (Gal-PAMAM) and poly(propyl ether amine) (Gal-PETIM) dendrimers as siRNA carriers using all-atom molecular dynamics simulations. This study revealed distinct complexation behavior for both the system in physiological (pH [~] 7) and high (pH [~] 10) environments. Electrostatic interactions dominated complexation, with PMF profiles revealing stronger binding affinity for Gal-PAMAM/siRNA at pH 7. siRNA displayed lower flexibility at pH 7 for both complexes, indicating enhanced stability. These findings suggest that Gal-PAMAM dendrimers at physiological pH hold promise for efficient siRNA delivery due to their superior complex stability and interaction strength. However, in polar solvents, Gal-PETIM exhibits hydrophobic behavior, enabling rapid delivery.

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