Chemotherapy efficiency increase via shock wave interaction with biological membranes: a molecular dynamics study

Application of ultrasound to biological tissues has been identified as a promising cancer treatment technique relying on temporal enhancement of biological membrane permeability via shock wave impact. In the present study, the effects of ultrasonic waves on a 1,2-dipalmitoyl-sn-phosphatidylcholine biological membrane are examined through molecular dynamics simulations. Molecular dynamics methods traditionally employ periodic boundary conditions which, however, restrict the total simulation time to the time required for the shock wave crossing the domain, thus limiting the evaluation of the effects of shock waves on the diffusion properties of the membrane. A novel method that allows capturing both the initial shock wave transit as well as the subsequent longer-timescale diffusion phenomena has been successfully developed, validated and verified via convergence studies. Numerical simulations have been carried out with ultrasonic impulses varying from 0.0 to 0.6 mPa s leading to the conclusion that for impulses ≥0.45 mPa s, no self-recovery of the bilayer is observed and, hence, ultrasound could be applied to the destruction of localized tumor cells. However, for impulses ≤0.3 mPa s, an increase in the transversal diffusivity of the lipids, indicating a consequent enhancement of drug absorption across the membrane, is initially observed followed by a progressive recovery of the initial values, thereby suggesting the advantageous effects of ultrasound on enhancing the chemotherapy efficiency.