Metal organic frameworks modified mesoporous silica nanoparticles (MSN): A nano-composite system to inhibit uncontrolled chemotherapeutic drug delivery from Bare-MSN

Mesoporous silica nanoparticles (MSN) are one of those compounds which have recently drawn attention in biomedical applications. But premature cargo leakage and uncontrolled release from bare MSN makes them unsuitable for drug delivery applications. Herein we report a new approach to modifying bare MSN to inhibit burst cargo release. The primary goal of this work was to combine metal organic framework (MOF) and MSN to form a nano-composite to build a hybrid drug delivery system to prevent premature drug release from bare-MSN. We first encapsulated Doxorubicin (DOX) inside MSN (MSN@DOX) and then used MSN@DOX to form composites through an in situ room temperature reaction in the aqueous medium with two biocompatible MOFs namely Fe-BTC and Zn-BTC. Two external triggering agents pH and liposome were used to conduct the drug release from MSN and the composite system. The pH-triggered release was conducted at three different pH 4, 6 and 7.4. MSN releases drug molecules within 2-3 h at all the pH whereas the composite system can control the release for more than four days. We also demonstrated that the drug release takes place for a significant period (4 days) when the newly developed DDS comes in contact with an artificial membrane such as liposomes. We evaluated the biological compatibility of these compounds in mammalian cell culture assay, and results show high biocompatibility of the DDS compared to earlier reports. The cytotoxicity study in HeLa and NIH3T3 cell line indicates that the composite systems are highly biocompatible and the cellular uptake studies of these composites using mouse embryonic fibroblast (NIH 3T3) cells and HeLa cells and DDS shows that the composite systems were successfully taken by cells without any morphological damages. MSN@DOX and MOF/MSN@DOX composites were characterized by transmission electron microscopy (TEM), bright field, confocal imaging, scanning electron microscopy (SEM), dynamic light scattering (DLS), X-ray powder diffraction (PXRD), IR-spectroscopy and thermogravimetric analysis (TGA). The results indicate that the newly prepared MOF/MSN@DOX DDS is superior to bare MSN based DDS. Overall, the present study highlights a new approach for controlled delivery of DOX from a MOF modified MSN, and hope that it will help to the further development of DDS based on composites materials shortly.