Molecular Modeling Of Transmembrane Delivery Of Anti-Cancer Drugs

The development of advanced delivery strategies for anticancer drugs that can permeate through cel ular membranes is urgently required for biomedical applications.Such strategies are helpful to improve the treatment efficiency of drugs and decrease the possible cytotoxicity.Furthermore,it is also of significance to understand the interaction mechanis m between drug molecules and cells and give a guide to the development of new drugs.In this work,we investigated the dynamic transmembrane behavior of paclitaxel(PTX),a powerful anticancer drug,under the combined impact of shock waves and nanobubbles,by using atomistic molecular dynamics simulations.Our simulations show that the PTX molecule experiences complicated motion modes during the action process with the membrane,as a consequence of its interplay with the lipid bilayer and water,under the joint effect of the shock wave and nanobubble.Moreover,it was found that the transmembra ne movement of PTX is closely associated with the conformation changes of PTX,as well as the structural changes of the membrane(e.g.,compression and poration in membrane).The nanobubble collapse induced by the shock wave,the proper PTX location with respect to the nanobubble,and a suitable nanobubble size and shock impulse are all necessary for the delivery of PTX into the cel.This work provides a molecular understanding of the interaction mechanism between drug molecules and cell membranes under the influence of shock waves and nanobubbles,and paves the way for exploiting targeted drug delivery systems that combine nanobubbles and ultrasound.