Hangrong Chen

Core/Shell Structured Hollow Mesoporous Nanocapsules: A Potential Platform for Simultaneous Cell Imaging and Anticancer Drug Delivery

A potential platform for simultaneous anticancer drug delivery and MRI cell imaging has been demonstrated by uniform hollow inorganic core/shell structured multifunctional mesoporous nanocapsules, which are composed of functional inorganic (Fe(3)O(4), Au, etc.) nanocrystals as cores, a thin mesoporous silica shell, and a huge cavity in between. The synthetic strategy for the creation of huge cavities between functional core and mesoporous silica shell is based on a structural difference based selective etching method, by which solid silica middle layer of Fe(2)O(3)@SiO(2)@mSiO(2) (or Au@SiO(2)@mSiO(2)) composite nanostructures was selectively etched away while the mesoporous silica shell could be kept relatively intact. The excellent biocompatibility of obtained multifunctional nanocapsules (Fe(3)O(4)@mSiO(2)) was demonstrated by very low cytotoxicity against various cell lines, low hemolyticity against human blood red cells and no significant coagulation effect against blood plasma. The cancer cell uptake and intracellular location of the nanocapsules were observed by confocal laser scanning microscopy and bio-TEM. Importantly, the prepared multifunctional inorganic mesoporous nanocapsules show both high loading capacity (20%) and efficiency (up to 100%) for doxorubicin simultaneously because of the formation of the cavity, enhanced surface area/pore volume and the electrostatic interaction between DOX molecules and mesoporous silica surface. Besides, the capability of Fe(3)O(4)@mSiO(2) nanocapsules as contrast agents of MRI was demonstrated both in vitro and in vivo, indicating the simultaneous imaging and therapeutic multifunctionalities of the composite nanocapsules. Moreover, the concept of multifunctional inorganic nanocapsules was extended to design and prepare Gd-Si-DTPA grafted Au@mSiO(2) nanocapsules for nanomedical applications, further demonstrating the generality of this strategy for the preparation of various multifunctional mesoporous nanocapsules.

Au capped magnetic core/mesoporous silica shell nanoparticles for combined photothermo-/chemo-therapy and multimodal imaging

Uniform Au NRs-capped magnetic core/mesoporous silica shell nanoellipsoids (Au NRs-MMSNEs) were prepared by coating a uniform layer of Au NRs on the outer surface of a magnetic core/mesoporous silica shell nanostructure, based on a two-step chemical self-assembly process. This multifunctional nanocomposite integrate simultaneous chemotherapy, photo-thermotherapy, in vivo MR-, infrared thermal and optical imaging into one single system. The obtained multifunctional nanoellipsoids showed very low cytotoxicity, and the cancer cell uptake and intracellular location of the nanoellipsoids were observed by confocal laser scanning microscopy and bio-TEM. Importantly, the prepared multifunctional nanoellipsoids showed high doxorubicin loading capacity and pH value-responsive release mainly due to the electrostatic interaction between DOX molecules and mesoporous silica surface. Besides, a synergistic effect of combined chemo- and photo-thermo therapy was found at moderate power intensity of NIR irradiation based on the DOX release and the photothermal effect of Au NRs.

A Facile One‐Pot Synthesis of a Two‐Dimensional MoS2/Bi2S3 Composite Theranostic Nanosystem for Multi‐Modality Tumor Imaging and Therapy

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Manganese oxide-based multifunctionalized mesoporous silica nanoparticles for pH-responsive MRI, ultrasonography and circumvention of MDR in cancer cells

Nano-biotechnology has been introduced into cancer theranostics by engineering a new generation of highly versatile hybrid mesoporous composite nanocapsules (HMCNs) for manganese-based pH-responsive dynamic T(1)-weighted magnetic resonance imaging (MRI) to efficiently respond and detect the tumor acidic microenvironment, which was further integrated with ultrasonographic function based on the intrinsic unique hollow nanostructures of HMCNs for potentially in vitro and in vivo dual-modality cancer imaging. The manganese oxide-based multifunctionalization of hollow mesoporous silica nanoparticles was achieved by an in situ redox reaction using mesopores as the nanoreactors. Due to the dissolution nature of manganese oxide nanoparticles under weak acidic conditions, the relaxation rate r(1) of manganese-based mesoporous MRI-T(1) contrast agents (CAs) could reach 8.81 mM(-1)s(-1), which is a 11-fold magnitude increase compared to the neutral condition, and is almost two times higher than commercial Gd(III)-based complex agents. This is also the highest r(1) value ever reported for manganese oxide nanoparticles-based MRI-T(1) CAs. In addition, the hollow interiors and thin mesoporous silica shells endow HMCNs with the functions of CAs for efficient in vitro and in vivo ultrasonography under both harmonic- and B-modes. Importantly, the well-defined mesopores and large hollow interiors of HMCNs could encapsulate and deliver anticancer agents (doxorubicin) intracellularly to circumvent the multidrug resistance (MDR) of cancer cells and restore the anti-proliferative effect of drugs by nanoparticle-mediated endocytosis process, intracellular drug release and P-gp inhibition/ATP depletion in cancer cells.

Hollow mesoporous organosilica nanoparticles: a generic intelligent framework-hybridization approach for biomedicine.

Chemical construction of molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both in vitro and in vivo.

Break‐up of Two‐Dimensional MnO2 Nanosheets Promotes Ultrasensitive pH‐Triggered Theranostics of Cancer

Chemically exfoliated two-dimensional MnO2 nanosheets are successfully modified with amino-polyethylene glycol as a theranostic platform for ultrasensitive stimuli-responsive theranostics of cancer. The highly dispersed MnO2 nanosheets exhibit a unique break-up in the mildly acidic microenvironment of tumor tissues, which could substantially enhance their in vitro and in vivo performances in T1 -weighted magnetic resonance imaging. Such a pH-triggered breaking-up behavior could further promote the fast release of loaded anticancer drugs for concurrent pH-responsive drug release and circumvent the multidrug resistance of cancer cells.

Colloidal HPMO Nanoparticles: Silica‐Etching Chemistry Tailoring, Topological Transformation, and Nano‐Biomedical Applications

Hybridization produces the better: Colloidal hollow periodic mesoporous organosilica nanoparticles (HPMO NPs) with tunable compositions and highly hybridized nanostructures are successfully synthesized by a simple, easily scale-up but versatile silica-etching chemistry (alkaline or HF etching) for their applications in nano-fabrication and nano-medicine.

Preparation of novel hollow mesoporous silica spheres and their sustained-release property

Novel hollow mesoporous silica spheres (HMSs) with uniform size and morphology have been successfully synthesized in a facile route using poly(vinylpyrrolidone) (PVP) and cetyltrimethylammonium bromide (CTAB) as co-templates at room temperature. XRD, N2 adsorption–desorption analysis, FE-SEM, and TEM are used for the characterization of the structure. The hexagonally ordered pore channels are formed on the shell. Ibuprofen (IBU) as a model drug is used to examine the storage capacity and the release behaviour of drug molecules. The storage capacity of hollow mesoporous silica spheres can reach 1133 ± 52.4 mg g−1 for ibuprofen, which is three times higher than that of conventional mesoporous materials previously reported (337 mg g−1), and the storage capacity is adjustable in a wide range. Furthermore, this system also shows a sustained-release behaviour. The release rates from the IBU-HMSs system (IBU stored in HMSs) increase with the decrease of pH values and the release process follows a Ficks law.

Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation

Organic/inorganic, hybrid, multifunctional, material-based platforms combine the merits of diverse functionalities of inorganic nanoparticles and the excellent biocompatibility of organic systems. In this work, superparamagnetic poly(lactic-co-glycolic acid) (PLGA) microcapsules (Fe(3)O(4)/PLGA) have been developed, as a proof-of-concept, for the application in ultrasound/magnetic resonance dual-modality biological imaging and enhancing the therapeutic efficiency of high intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo. Hydrophobic Fe(3)O(4) nanoparticles were successfully integrated into PLGA microcapsules by a typical double emulsion evaporation process. In this process, highly dispersed superparamagnetic Fe(3)O(4)/PLGA composite microcapsules with well-defined spherical morphology were obtained with an average diameter of 885.6 nm. The potential of these microcapsules as dual contrast agents for ultrasonography and magnetic resonance imaging were demonstrated in vitro and, also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite microcapsules were administrated into rabbits bearing breast cancer model for the evaluation of the in vivo HIFU synergistic ablation efficiency caused by the introduction of such microcapsules. Our results showed that the employment of the composite microcapsules could efficiently enhance ultrasound imaging of cancer, and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition, pathological examination was systematically performed to detect the structural changes of the target tissue caused by HIFU ablation. This finding demonstrated that successful introduction of these superparamagnetic microcapsules into HIFU cancer surgery provided an alternative strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy of cancer.

Perfluorohexane-encapsulated mesoporous silica nanocapsules as enhancement agents for highly efficient high intensity focused ultrasound (HIFU).

An inorganic enhancement agent (EA) for high-intensity focused ultrasound (HIFU) imaging based on mesoporous silica nanocapsules is presented. The pronounced coagulative necrosis effects demonstrate, both in vitro and in vivo, that the EA can be developed as a highly promising theranostic agent for effective HIFU imaging and therapy owing to its high stability, efficient perfluorohexane loading and release, enhanced tumor ablation capability, and easy uptake by target tissues. Copyright