Multifunctional phase-change hollow mesoporous Prussian blue nanoparticles as a NIR light responsive drug co-delivery system to overcome cancer therapeutic resistance

Developing novel stimuli-responsive systems to optimize the co-delivery and concurrent controlled release of different anticancer drugs is highly pursued for reducing the probability of evolution of therapeutic resistance, which is the major cause of cancer mortality. In this work, we report a novel NIR light responsive drug co-delivery system based on hollow mesoporous Prussian blue nanoparticles (HMPBs) and a phase change material (PCM, such as 1-tetradecanol which has a melting point around 38 °C). The fabrication of this PCM@HMPB system simply involves filling the hollow interior and mesoporous shell of the HMPBs with PCM molecules, which acted as both a thermosensitive gatekeeper and a medium for loading both hydrophilic and hydrophobic anticancer drugs. The photothermal effect of the HMPBs under NIR light irradiation would induce the PCM to go through processes of melting and escaping from the HMPBs, concurrently releasing the encapsulated anticancer drugs into the surrounding medium. Notably, the as-prepared (PCM + drugs)@HMPB system could achieve near "zero release" of both hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic camptothecin (CPT), as well as precise "on" or "off" drug delivery with various NIR light treatments in vitro to efficiently induce cell apoptosis. More importantly, according to the phenomenon that generated heat could improve drug absorption by increasing the cell metabolism and membrane fluidity, the (PCM + drugs)@HMPB system revealed significant photothermal-chemo synergistic effects against HeLa cancer cells. Therefore, the as-prepared (PCM + drugs)@HMPB system has good potential as a versatile NIR light responsive co-delivery platform of both hydrophobic and hydrophilic anticancer drugs for targeting adaptive therapeutic resistance as well as synergistic photothermal-chemo cancer treatment.