Studies On Near-infrared Light- And PH-responsive Controlled Release Based On Graphene Capped Mesoporous Silica Nanoparticles

Stimuli-responsive controlled-release systems have great potential in cancer treatment in terms of maintaining drug concentration within the therapeutic window by controlling the drug release rate, which would result in enhancing drug therapeutic effect and minimizing adverse effects of cytotoxic drugs. With the distinctive characteristics of stable mesostructure, biocompatibility, large loading capacity, and ease of surface functionalization, mesoporous silica nanoparticles have attracted great attention in a stimuli-responsive capped/gated release mechanism. Graphene nanomaterial is a new two-dimensional material with every carbon atoms sp2 hybridized exposed on its surface, owing to its biocompatibility, unique structure, and relatively low cost, has now attracted great attention from scientific communities. Herein, we chose mesoporous silica nanoparticles as drug carrier and functionalized nano-graphene nanomaterials as gated molecules to design the near-Infrared light- and p H-responsive release system. The main research aspects are as follow:1. Near-infrared light-responsive controlled release system based on reduced graphene oxide capped mesoporous silica nanoparticlesGraphene oxide has been reduced for enhanced and modified optical properties, such as photothermal effect, resulting in the synthesis of reduced graphene oxide. In this paper, we report the assembly of reduced graphene oxide and silica grafted with alkyl chains to develop a new class of drug carriers which are able to deliver the loaded drug molecules in living cells upon near-infrared light exposure. This novel drug carrier consists of a structure formed by the noncovalent interaction of reduced graphene oxide caps and alkyl chains on the surface of mesoporous silica. The capping of reduced graphene oxide to the mesoporous silica effectively blocks the pore mouths in the absence of a near-infrared light. Conversely, and very importantly, the photothermal heating effect of reduced graphene oxide leads to a rapid rise in the local temperature upon application to near-infrared light, resulting in the weakening of the reduced graphene oxide/alkyl chains noncovalent interaction. The reduced graphene oxide will then get off from the mesoporous silica surface, and the pores were uncapped. This uncapping mechanism makes it possible to release the loaded drug molecules by an irradiation with near-infrared light. In the present study, such noncovalent assembly was examined by the use of doxorubicin as a model drug for near-infrared light-responsive intracellular controlled release studies. The cell viability results showed that the nanocomposites were fairly biocompatible and indeed served as a drug-carrier for intracellular controlled release. Moreover, the DOX-loaded nanocomposites exhibited a remarkably enhanced efficiency in killing cancer cells. We believed that the stimuli-responsive controlled MSN release system based on noncovalent assembly could play an important role in the development intracellular delivery nanodevices in vivo in the near future.2. p H-responsive controlled release system based on graphene quantum dots capped mesoporous silica nanoparticlesAs newcomers to the world of graphene nanomaterials, smaller graphene quantum dots exhibit more excellent biocompatibility and water dispersion than reduced graphene oxide. More importantly, graphene quantum dots exhibit strong photoluminescence property. In this paper, the use of biocompatible graphene quantum dots as caps on the surface of mesoporous silica nanoparticles for the design of intelligent on-demand molecular delivery and cell imaging system is described. These nano-carrier exhibited low cytotoxicity toward the cells and strong luminescence both in vitro. A further loading of anticancer drug endowed the fluorescent material with therapeutic functions. It was found that changing the p H to mildly acidic condition at physiological temperature caused the dissociation of the nanocomposites and release of a large number of DOX from the nanospheres. Moreover, the DOX-loaded nanocomposites exhibited a remarkably enhanced efficiency in killing cancer cells. The endocytosis and the efficient drug release properties of the system were confirmed by luminescence microscopy. Overall, we believe that the well-designed nanocomposites are promising for a simultaneous bioimaging and drug delivery system in vivo in the near future, which show more potential for clinical application.