Controllable drug release system based on phase change molecules as gatekeepers for bimodal tumor therapy with enhanced efficacy

Abstract

A mixture of anticancer drug doxorubicin hydrochloride (DOX) and 1-tetradecanol (TD) are co-loaded into core–shell structured Cu₉S₅@mSiO₂ nanoparticles to achieve bimodal tumor therapy with enhanced efficacy. TD, a kind of phase change molecule with a melting temperature (T_m) of 39 °C, acts as a gatekeeper to control DOX release. Cu₉S₅ is a kind of good photothermal agent and has the advantage of a high photothermal conversion efficiency, which has a thermal effect on TD. Cu₉S₅ NCs at a concentration of 312.5 ppm can elevate its temperature by 28.6 °C in 5 min when the system is irradiated by a 980 nm laser (0.5 W cm⁻²). When the temperature of the system is higher than 39 °C, TD can melt and DOX will release from the pores. Besides NIR-triggered release, the DOX release is also controlled by pH. Synergistic NIR-triggered and pH-triggered DOX release prevents the premature release of drug molecules (<4% of the whole loaded DOX in 24 h) in neutral conditions without irradiation. However, upon irradiation in acidic conditions (pH = 5.0), the release of the whole loaded DOX could reach 32.6%. Therefore, this versatile combination of photothermal therapy and chemotherapy makes the application of multifunctional drug delivery systems possible.