A unique mesoporous silica nanoparticles (MSNs)-based theranostic platform with ultrasmall iron oxide nanoparticles (NPs) confined within mesopore network has been developed by a facile but efficient physical-vapor-infiltration (PVI) method. The highly dispersed Fe species within mesopore channels can synchronously function as the non-toxic contrast agents for highly efficient T₁-weighted MR imaging, and as anchoring sites for anti-cancer drug molecule loading and pH-responsive release based on the special metal-ligand coordination bonding between the Fe species and drug molecules. Moreover, the obtained Fe-MSNs exhibit favorable biocompatibility, enhanced chemotherapeutic efficacy and concurrently diminished side effects due to the non-specific attack of chemotherapeutic drugs, as well as the capability in circumventing the multidrug resistance (MDR) of cancer cells and suppressing the metastasis of tumor cells in vitro and in vivo. This pH-resoponsive theranostic agent provides a new promising MSNs-based anti-cancer nanomedicine for future biomedical application.

Construction of multifunctional stimuli-responsive nanosystems intelligently responsive to inner physiological and/or external irradiations based on nanobiotechnology can enable the on-demand drug release and improved diagnostic imaging to mitigate the side-effects of anticancer drugs and enhance the diagnostic/therapeutic outcome simultaneously. Here, a triple-functional stimuli-responsive nanosystem based on the co-integration of superparamagnetic Fe₃O₄ and paramagnetic MnO_x nanoparticles (NPs) onto exfoliated graphene oxide (GO) nanosheets by a novel and efficient double redox strategy (DRS) is reported. Aromatic anticancer drug molecules can interact with GO nanosheets through supramolecular π stacking to achieve high drug loading capacity and pH-responsive drug releasing performance. The integrated MnO_x NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH-responsive and reduction-triggered T₁-weighted magnetic resonance imaging (MRI). Superparamagnetic Fe₃O₄ NPs can not only function as the T₂-weighted contrast agents for MRI, but also response to the external magnetic field for magnetic hyperthermia against cancer. Importantly, the constructed biocompatible GO-based nanoplatform can inhibit the metastasis of cancer cells by downregulating the expression of metastasis-related proteins, and anticancer drug-loaded carrier can significantly reverse the multidrug resistance (MDR) of cancer cells.

The purpose of this study was to develop a high-drug-loading nanoemulsion by self-assembly to improve the oral absorption of high dosing poorly water-soluble drugs. Probucol was selected as a model drug and the probucol-loaded self-assembled nanoemulsion (PSN) was prepared and characterized. Moreover, the intestinal absorption and in vivo pharmacokinetic behavior of PSN were evaluated in rats after oral administration. The experimental results indicated that PSN was nanometer-sized droplets with the mean diameter of 40.32 ± 0.31 nm and polydispersity index of 0.184 ± 0.005. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free drug suspension, the intestinal absorption of PSN was not significantly increased in duodenum, but obviously enhanced 3.62- and 13.1-fold in jejunum and ileum, respectively. In particular, the in vivo pharmacokinetic results indicated that the oral bioavailability of probucol was greatly improved 8.97-fold by PSN. Thereby, the high-drug-loading self-assembled nanoemulsion was very effective in enhancing the oral absorption of high-dosing poorly water-soluble drugs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1301–1306, 2013

A novel drug-formulation protocol is developed to solve the delivery problem of hydrophobic drug molecules by using inorganic mesoporous silica nanocapsules (IMNCs) as an alternative to traditional organic emulsions and liposomes while preserving the advantages of inorganic materials. The unique structures of IMNCs are engineered by a novel fluoride-silica chemistry based on a structural difference-based selective etching strategy. The prepared IMNCs combine the functions of organic nanoemulsions or nanoliposomes with the properties of inorganic materials. Various spherical nanostructures can be fabricated simply by varying the synthetic parameters. The drug loading amount of a typical highly hydrophobic anticancer drug-camptothecin (CPT) in IMNCs reaches as high as 35.1 wt%. The intracellular release of CPT from carriers is demonstrated in situ. In addition, IMNCs can play the role of organic nanoliposome (multivesicular liposome) in co-encapsulating and co-delivering hydrophobic (CPT) and hydrophilic (doxorubicin, DOX) anticancer drugs simultaneously. The co-delivery of multi-drugs in the same carrier and the intracellular release of the drug combinations enables a drug delivery system with efficient enhanced chemotherapeutic effect for DOX-resistant MCF-7/ADR cancer cells. The special IMNCs-based “inorganic nanoemulsion”, as a proof-of-concept, can also be employed successfully to encapsulate and deliver biocompatible hydrophobic perfluorohexane (PFH) molecules for high intensity focused ultrasound (HIFU) synergistic therapy ex vivo and in vivo. Based on this novel design strategy, a wide range of inorganic material systems with similar “inorganic nanoemulsion or nanoliposome” functions will be developed to satisfy varied clinical requirements.