Tunable Intracellular Degradable Periodic Mesoporous Organosilica Hybrid Nanoparticles for Doxorubicin Drug Delivery in Cancer Cells.

In this work, a dual (pH and redox)-sensitive cystamine-integrated periodic mesoporous organosilica (Cys-PMO) hybrid nanoparticle has been developed and subsequently loaded with doxorubicin (Dox) as an anticancer drug for intracellular cancer drug delivery. The formation of Cys-PMO was confirmed by FTIR, 13C (CP-MAS), and 29Si MAS NMR spectroscopic techniques. X-ray diffraction and transmission electron microscopy confirmed that the Cys-PMO hybrid nanoparticles possessed mesoscopically ordered 2D hexagonal (P6mm) symmetry with cylindrical shape morphology. The N2 sorption isotherm showed that the Cys-PMO hybrid nanoparticles have a large surface area (691 m2 g-1), pore diameter (3.1 nm), and pore volume (0.59 cm3 g-1). As compared to conventional mesoporous silica materials and other PMO nanoparticles, the developed Cys-PMO hybrid nanoparticles have the capability of holding a high Dox content 50.6% (15.2 mg of Dox per 30 mg of Cys-PMO) at an optimized concentration (20 mg Dox) and avoid premature drug release under extracellular conditions. In vitro, the treatment of HeLa cells with Dox-encapsulated Cys-PMO hybrid nanoparticles results in a significantly greater cytotoxicity in response to intracellular acidic pH and a redox environment due to the degradation of disulfide bonds available in the framework of Cys-PMO hybrid nanoparticles. Further, confocal microscope images show the colocalization of Dox-loaded Cys-PMO hybrid nanoparticles inside the HeLa cells. Upon internalization inside HeLa Cells, the Cys-PMO use intracellular pH and redox environments to release Dox to the nucleus. Thus, the pH and reduction sensitivity of Cys-PMO hybrid nanoparticles make them suitable for intracellular drug delivery applications.