Hongmin Chen

RGD Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors

Ferritin (FRT) is a major iron storage protein found in humans and most living organisms. Each ferritin is composed of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD-integrin αvβ3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein, we showed that after being precomplexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49 wt %). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.

Ferritin Nanocages To Encapsulate and Deliver Photosensitizers for Efficient Photodynamic Therapy against Cancer

Photodynamic therapy is an emerging treatment modality that is under intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner. Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high (1)O2 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as ~60 wt % (i.e., 1.5 mg of ZnF16Pc can be loaded on 1 mg of RFRTs), which far exceeds those reported previously. Despite the high loading, the ZnF16Pc-loaded RFRTs (P-RFRTs) show an overall particle size of 18.6 ± 2.6 nm, which is significantly smaller than other PS-nanocarrier conjugates. When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 ± 4.07 at 24 h), a good tumor inhibition rate (83.64% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.

Nanoscintillator-Mediated X-ray Inducible Photodynamic Therapy for In Vivo Cancer Treatment

Photodynamic therapy is a promising treatment method, but its applications are limited by the shallow penetration of visible light. Here, we report a novel X-ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised of a core of a nanoscintillator and a mesoporous silica coating loaded with photosensitizers, converts X-ray photons to visible photons to activate the photosensitizers and cause efficient tumor shrinkage.

Gd-encapsulated carbonaceous dots with efficient renal clearance for magnetic resonance imaging.

Nanoprobes for MRI and optical imaging are demonstrated. Gd@C-dots possess strong fluorescence and can effectively enhance signals on T1 -weighted MR images. The nanoprobes have low toxicity, and, despite a relatively large size, can be efficiently excreted by renal clearance from the host after systemic injection.

One-step synthesis of monodisperse and hierarchically mesostructured silica particles with a thin shell.

Monodisperse, uniform, and hierarchically mesostructured silica particles with a thin shell have been fabricated via one-step synthesis using dodecanethiol (C(12)-SH) and CTAB as dual templates. A series of hierarchically mesostructured silica particles with a morphology similar to that of pomegranate can be obtained by simply adjusting the mass ratio of C(12)-SH to CTAB. When the mass ratio is increased, a mesophase transformation occurs from an ordered 2D hexagonal structure to a mesostructured cellular foam in the core of the hierarchically mesoporous silica particles. These unique silica particles are characterized by small-angle X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), and nitrogen adsorption-desorption measurements. The formation mechanism of the hierarchically mesostructured silica particles with a thin shell is proposed according to the experimental results. Synergistic self-assembly of C(12)-SH and CTAB in the solution is believed to play a key role in mediating the formation of these hierarchical silica mesostructures, and the hydrophobic dodecanethiol can act as both the swelling agent for CTAB micelles and coagent for the formation of a microemulsion with CTAB micelles. This synthesis method is simple, straightforward, and suitable for the preparation of the other biomineral nanostructures that are unique scaffolds in biological, medical, and catalytic applications.

Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging.

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr3+ near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr3+ nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

Glycine-assisted hydrothermal synthesis of peculiar porous α-Fe2O3 nanospheres with excellent gas-sensing properties

In this work, peculiar porous alpha-Fe(2)O(3) nanospheres were fabricated by a glycine-assisted hydrothermal method. They have large mesopores (ca. 10nm) in the core and small mesopores (<4 nm) in the shell. To our best knowledge, there have been so far no reports on the synthesis of such peculiar porous alpha-Fe(2)O(3) nanospheres. X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy and transmission electron microscopy were employed to characterize the obtained Fe(2)O(3) nanospheres. Effects of preparation conditions, such as reactants, reaction temperature and reaction duration, were investigated on the morphology and structure of Fe(2)O(3) nanospheres. It was shown that the morphology and structure could be readily controlled by the time and temperature of hydrothermal treatment. The formation mechanism was proposed based on experimental results, which shows that glycine molecules play an important role in the formation of the morphology and porous structure of alpha-Fe(2)O(3). The alpha-Fe(2)O(3) porous nanospheres were used as gas sensing layer, and exhibited excellent gas-sensing properties to ethanol in terms of response and selectivity. The sensors showed good reproducibility and stability as well as short response (9 s) and recovery time (43 s) even at an ethanol concentration as low as 50 ppm. The gas-sensing properties of porous alpha-Fe(2)O(3) nanospheres are also significantly better than those of previously reported Fe(2)O(3) nanoparticles (ca. 30 nm). The sensitivity of the former is over four times higher than that of the latter at varied ethanol concentrations. The gas-sensing mechanism was discussed in details. Both fast response and steady signal make these peculiar nanostructures a promising candidate for ethanol detection.

Porous magnetic manganese oxide nanostructures: Synthesis and their application in water treatment

Magnetic manganese oxide nanostructures are fabricated at room temperature by mixing a KMnO(4) solution and oleic acid capped Fe(3)O(4) particles. Oleic acid molecules capped Fe(3)O(4) particles are oxidized by potassium permanganate (KMnO(4)) in an aqueous solution to produce porous magnetic manganese oxide nanostructures. The synthesis technique can be extended to other MnO(x) structures with composition of different nanocrystals, such as quantum dots, noble metal crystals which may have important applications as catalysts, adsorbents, electrodes and advanced materials in many scientific disciplines. Transmission electron microscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, and nitrogen adsorption-desorption measurements are employed to characterize the structures. As an adsorbent in water treatment, the nanostructures possess a large adsorption capability and high organic pollutant removal rates due to the large surface area and pore volume. The nanostructures are recyclable as their adsorption capability can be recovered by combustion. Furthermore, the strong magnetism exhibited by the structures provides an easy and efficient separation means in wastewater treatment under an external magnetic field.

Fine control over the morphology and structure of mesoporous silica nanomaterials by a dual-templating approach

Mesoporous silica nanomaterials with varied morphologies and pore structures, including nanospheres, nanoellipsoids, helical nanorods and multi-lamellar nanovesicles, were synthesized by using cetyltrimethylammonium bromide (CTAB) and sodium bis(2-ethylhexyl) sulfosuccinate (AOT) as co-templates.

Iron oxide nanoparticle encapsulated diatoms for magnetic delivery of small molecules to tumors.

Small molecules can be co-loaded with iron oxide nanoparticles onto diatoms. With an external magnetic field, the diatoms, after systemic administration, can be attracted to tumors. This study suggests a great potential of diatoms as a novel and powerful therapeutic vehicle.