Synthesis of pH-Responsive Biodegradable Mesoporous Silica–Calcium Phosphate Hybrid Nanoparticles as a High Potential Drug Carrier

Biodegradability is one of the most critical issues for silica-based nanodrug delivery systems because they are crucial prerequisites for the successful translation in clinics. In this work, a novel mesoporous silica-calcium phosphate (MS-CAP) hybrid nanocarrier with a fast pH-responsive biodegradation rate was developed by a one-step method, where CAP precursors (Ca²⁺ and PO₄³⁻) were incorporated into silica matrix during the growth process. The morphology and structure of MS-CAP were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), N₂ adsorption-desorption isotherms, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. Furthermore, the drug loading and the release behavior of MS-CAP have been tested. TEM and inductively coupled plasma-optical emission spectrometry results indicated that the pH-responsive biodegradation of MS-CAP was so fast that could be almost finished within 24 h owing to the easy dissolution of CAP embedded in the particle and the escape of Ca²⁺ from the structure of Si-O-Ca in acid environment. The MS-CAP exhibited a high doxorubicin (DOX) entrapment efficiency (EE) of 97.79%, which was about fourfold higher compared with that of pure mesoporous silica nanoparticles, and our density functional theory calculational results suggested that the higher drug EE of MS-CAP would originate from the strong interaction between calcium in the particle and carboxylate group of DOX. The loaded DOX was effectively released, with a cumulative release as high as 98.06% within 48 h at pH 4.5 in buffer solution, owing to the rapid degradation of MS-CAP. The obtained results indicated that the as-synthesized MS-CAP could act as a promising drug delivery system and would have a hopeful prospect in the clinical translation.