Magnetically Triggered Multidrug Release by Hybrid Mesoporous Silica Nanoparticles

The treatment of complex diseases such as cancer pathologies requires the simultaneously administration V of several drugs in order to improve the effectiveness of the therapy and overwhelm the defensive mechanisms of tumor cells, responsible of the apparition of multidrug resistance (MDR). In this manuscript, a novel nanodevice able to perform remotely controlled release of small molecules and proteins in response to an alternating magnetic field has been presented. This device is based on mesoporous silica nanoparticles with iron oxide nanocrystals encapsulated inside the silica matrix and decorated on the surface with a thermoresponsive copolymer of poly(ethyleneimine)-b-poly(N-isopropylacrylamide) (PEI/NIPAM). The polymer structure has been designed with a double purpose, to act as temperature-responsive gatekeeper for the drugs trapped inside the silica matrix and, on the other hand, to retain proteins into the polymer shell by electrostatic or hydrogen bonds interactions. The nanocarrier traps the different cargos at low temperatures (20 C) and releases the retained molecules when the temperature exceeds 35-40 degrees C following different kinetics. The ability to remotely trigger the release of different therapeutic agents in a controlled manner in response to a nontoxic and highly penetrating external stimulus as alternating magnetic field, along with the synergic effect associated to hyperthermia and chemotherapy, and the possibility to use this nanocarrier as contrast agent in magnetic resonance imagining (MM) convert this nanodevice in an excellent promising candidate for further studies for oncology therapy.