Programmable Delivery of Synergistic Cancer Drug Combinations Using Bicompartmental Nanoparticles

Abstract

Delivery of multiple therapeutics has become a preferred method of treating cancer, albeit differences in the biodistribution and pharmacokinetic profiles of individual drugs pose challenges in effectively delivering synergistic drug combinations to and at the tumor site. Here, bicompartmental Janus nanoparticles comprised of domains are reported with distinct bulk properties that allow for independent drug loading and release. Programmable drug release can be triggered by a change in the pH value and depends upon the bulk properties of the polymers used in the respective compartments, rather than the molecular structures of the active agents. Bicompartmental nanoparticles delivering a synergistic combination of lapatinib and paclitaxel result in increased activity against HER2+ breast cancer cells. Surprisingly, the dual drug loaded particles also show significant efficacy toward triple negative breast cancer, even though this cancer model is unresponsive to lapatinib alone. The broad versatility of the nanoparticle platform allows for rapid exploration of a wide range of drug combinations where both their relative drug ratios and temporal release profiles can be optimized.Bicompartmental Janus nanoparticles offer an ability to delivery multiple therapeutics from a single platform. Responsive to pH, the decoupled release kinetics from each compartment are dependent upon the bulk polymer properties. These qualities allow for the further development of combination therapy platforms capable of efficiently delivering synergistic drug combinations to tumors, dependent on dosing amounts and schedule.