Dual pH-/Thermoresponsive Shell-Cross-Linked Magnetic Mesoporous Nanospheres for Doxorubicin Delivery and In Vitro/In Vivo Cancer Treatment

Abstract

Engineered nanomaterials have been explored for chemotherapeutic drug delivery systems toward improved therapeutic effects. In this study, magnetic nanospheres consisting of MCM-41 formed onto iron oxide nanoparticles (MIO NPs) to form MMCM with cross-linked shells of Pluronic F127 (PF) and polyethylenimine (PEI) to form (MMFPEI NSs) nanospheres were synthesized. These nanospheres were loaded with doxorubicin (DOX) anticancer drug for drug-controlled release and therapeutic efficacy evaluations in mice. Nanoscale/core–shell MMFPEI NSs were successfully formed as indicated by the TEM analysis. The microstructural analysis revealed the presence of three peaks corresponding to indexed reflections (100), (110), and (200) of MCM-41. The MMFPEI NSs displayed a pH-/thermoresponsive drug release of 84.76% under a simulated tumor microenvironment. Principally, the Peppas-Sahlin, Weibull, and Korsmeyer-Peppas models, respectively, provided the best fitting for our drug delivery system with the highest correlation degree of coefficient (R2) and the lowest AIC. The kinetics studies for diffusion exponent indicated that the MMFPEI NSs possessed predominantly Fickian diffusion behavior. The growth retardation results of HepG2 cells showed that when compared with free DOX, the MMFPEI-DOX NSs exhibited statistically significant stronger cell inhibition efficacy at the dosages of 2, 5, and 10 μg/mL after 24 and 48 h of incubation. According to the in vivo therapeutic assessments, the tumor sizes upon inoculation with PBS, MMFPEI NSs, PBS-DOX, and MMFPEI-DOX NSs were 1302.7, 1165.6, 830.9, and 382.6 mm3, respectively. Therefore, the formulated nanospheres have great probable for drug delivery in cancer therapy to overcome the limits of traditional chemotherapy.