A multi-scale molecular dynamics simulation of PMAL facilitated delivery of siRNA

Abstract

The capability of silencing genes makes small interfering RNA (siRNA) appealing for curing fatal diseases such as cancer and viral infections. In the present work, we chose a novel amphiphilic polymer, PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine), as the siRNA carrier, and conducted steered molecular dynamics simulations, together with traditional molecular dynamics simulations, to explore how PMAL facilitates the delivery of siRNA. It was shown that the use of PMAL reduced the energy barrier for siRNA to penetrate lipid bilayer membranes, as confirmed by the experimental work. The simulation of the transmembrane process revealed that PMAL can punch a hole in the lipid bilayer and form a channel for siRNA delivery. Monitoring of the structural transition further showed the targeting of siRNA through the attachment of PMAL encapsulating siRNA to a lipid membrane. The delivery of siRNA was facilitated by the hydrophobic interaction between PMAL and the lipid membrane, which favored the dissociation of the siRNA–PMAL complex. The above simulation established a molecular insight of the interaction between siRNA and PMAL and was helpful for the design and applications of new carriers for siRNA delivery.