Release kinetics study of fatty acids eutectic mixture gated mesoporous carbon nanoparticles for chemo-photothermal therapy

Precise drug release in tumor sites is the key to improving the curative effect and reducing the toxic and side effects of chemotherapy. Herein, mesoporous carbon nanoparticles (MCN) and thermo-sensitive biocompatible phase change material (PCM) composed of stearic acid and lauric acid eutectic mixture were integrated for achieving the "on-demand" release of poorly soluble drug mercaptopurine (MP). MCN endowed the system with the potential of photothermal therapy (PTT) as well as high drug-loading efficiency. Fatty acids eutectic mixture with a well-designated melting point of 40 °C was used as the gatekeeper to trap MP in the mesopores of MCN. As expected, the drug was not released until PCM was melted down by the heat generated under NIR irradiation, thus inhibiting the premature release of drugs at body temperature. Notably, the release kinetic study results of inactivated MCN@MP/PCM system demonstrated the premature release of the drug was caused by diffusion, and adjusting the added PCM amounts just changed the controlled release effect of drugs without affecting release mechanisms. According to the cellular uptake, cytotoxicity and anti-tumor spheroids assays, the prominent NIR-triggered drug release property and photothermal effect of MCN@MP/PCM enhanced the antitumor activity, possessing the satisfied synergistic chemo-photothermal antitumor effect with a combination index of 0.554. This work provides a comprehending basis for designing a better-controlled release system to realize a safer and more efficient synergistic antitumor effect.