Magnetically Triggered Multidrug Release by Hybrid Mesoporous Silica Nanoparticles

Abstract

The treatment of complex diseases such as cancer pathologies requires the simultaneously administration 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 °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 (MRI) convert this nanodevice in an excellent promising candidate for further studies for oncology therapy.

Controlled release and intracellular protein delivery from mesoporous silica nanoparticles

“…Vallet-Regí and coworkers were able to demonstrate the release of both proteins and small molecules in response to an alternating magnetic field and changes in temperature [55]. Magnetic iron oxide nanocrystals were imbedded inside the silica matrix of MSN and the MSN surface was functionalized with the thermally responsive block copolymer poly(ethyleneimine)-b-poly(N-isopropylacrylamide) (PEI/PNIPAM).…”

“…As temperature increased above the LCST, the pores opened and a significant increase in protein release occurred due to polarity inversion (hydrophilic to hydrophobic transition) and three-dimensional polymeric changes in the network. Thus, the authors concluded that the phase transition of the polymer acted as the gatekeeper, allowing or preventing the release of macromolecules attached into the polymer branches [55].…”

“…The release of these cargos can be controlled, and if the system is properly designed, cargo release can be triggered remotely with nontoxic and penetrating stimuli like an alternating magnetic field. The synergic effect associated with chemotherapy and hyperthermia make MSNs promising candidates for oncology therapy [55]. Below are several choice examples describing the potential of MSNs for therapeutic protein delivery.…”

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…It is clear that developing novel multifunctional vectors, which transform their physicochemical properties in response to various stimuli in a timely and spatially controlled manner, is highly desired to translate the promise of gene therapy for clinical success. The temperature-sensitive NPs have been identified, many of them including heat activable iron oxide and thermosensitive polymers [537 -547] , silica NPs [542,544,548] , liposomes [548 -550] , micelles [551] , multifunctional NPs containing both CdTe QDs, and Fe 3 O 4 magnetic particles [552] .…”

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

“…Over the past several years, significant advancements have been made with regards to the synthesis and tunability of functionalized drug carriers, switches, membranes, containers, pumps, and valves. 1,3,[5][6][7][8][11][12][13][26][27][28][29][30] State of the art implantable micro-devices include reservoir-based systems, controlled-release microchips, and various electrically powered microsystems. 1,2,10,31 Osmotic pumps present a convenient and reliable cost-effective drug delivery method capable of replacing repeated injections of soluble and poorly soluble drugs 32,33 for the treatment of chronically debilitating diseases.…”