Polymer-Scaffolded Synthesis of Periodic Mesoporous Organosilica Nanomaterials for Delivery Systems in Cancer Cells

We developed four types of para-phenylene-bridged periodic mesoporous organosilica NPs (p-P PMO NPs) with tailored physical parameters including size, morphology, porosity, and surface area using a new polymer-scaffolding approach. The particles have been formulated to facilitate the codelivery of small-molecule hydrophobic/hydrophilic cargos such as model anticancer drugs (i.e., doxorubicin hydrochloride (DOX) and O6-benzylguanine) and model fluorescent dyes (i.e., rhodamine 6G and Nile red). p-P PMO NPs were synthesized via a cetyltrimethylammonium bromide (CTAB)-directed sol-gel process using two different organic solvents and in the presence of polymeric scaffolding constituents that led to morphologically distinct PMO NPs despite using the same organosilane precursors. After the formulation process, the polymeric scaffolding agent was conveniently washed away from the PMO NPs. Extensive analyses were used to characterize the physicochemical attributes of the PMO NPs such as their chemical composition, morphologies, etc. Spherical and rod-shaped PMOs of diameters ranging between 79 and 342 nm, surface areas between 770 and 1060 m2/g, and pore volumes between 0.79 and 1.37 cm3/g were prepared using the polymer-scaffolding approach. The performance of these materials toward drug-loading capacity, cytotoxicity, and cancer cell internalization was evaluated. Interestingly, the designed particles exhibited significantly high payloads of drugs and dyes (up to 78 and 94%, respectively). Cellular studies also demonstrated exceptional biocompatibility and marked internalization into both human breast cancer MCF-7 and glioblastoma U-87 MG cells. Further, DOX also possessed a noticeable release from particles and accumulation in cell nuclei with increased incubation time in vitro. Ultimately, this work validates the controlled design and synthesis of PMO NPs using a polymer-scaffolding approach and highlights the potential of these materials as excellent delivery systems for combination therapy with high loading capability to improve the therapeutic index for cancers.