Zhiyao Hou

In Vivo Multimodality Imaging and Cancer Therapy by Near-Infrared Light-Triggered trans-Platinum Pro-Drug-Conjugated Upconverison Nanoparticles

Controlling anticancer drug activity and release on demand is very significant in cancer therapy. The photoactivated platinum(IV) pro-drug is stable in the dark and can be activated by UV light. In this study, we develop a multifunctional drug delivery system combining upconversion luminescence/magnetic resonance/computer tomography trimodality imaging and NIR-activated platinum pro-drug delivery. We use the core-shell structured upconversion nanoparticles to convert the absorbed NIR light into UV to activate the trans-platinum(IV) pro-drug, trans,trans,trans-[Pt(N3)2(NH3)(py)(O2CCH2CH2COOH)2]. Compared with using the UV directly, the NIR has a higher tissue penetration depth and is less harmful to health. Meanwhile, the upconversion nanoparticles can effectively deliver the platinum(IV) pro-drugs into the cells by endocytosis. The mice treated with pro-drug-conjugated nanoparticles under near-infrared (NIR) irradiation demonstrated better inhibition of tumor growth than that under direct UV irradiation. This multifunctional nanocomposite could be used as multimodality bioimaging contrast agents and transducers by converting NIR light into UV for control of drug activity in practical cancer therapy.

Up-Conversion Cell Imaging and pH-Induced Thermally Controlled Drug Release from NaYF4:Yb3+/Er3+@Hydrogel Core–Shell Hybrid Microspheres

In this study, we report a new controlled release system based on up-conversion luminescent microspheres of NaYF(4):Yb(3+)/Er(3+) coated with the smart hydrogel poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (P(NIPAM-co-MAA)) (prepared using 5 mol % of MAA) shell. The hybrid microspheres show bright up-conversion fluorescence under 980 nm laser excitation, and turbidity measurements show that the low critical solution temperature of the polymer shell is thermo- and pH-dependent. We have exploited the hybrid microspheres as carriers for Doxorubicin hydrochloride (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is pH-triggered thermally sensitive. Changing the pH to mildly acidic condition at physiological temperature deforms the structure of the shell, causing the release of a large number of DOX from the microspheres. The drug-loaded microspheres exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells. The endocytosis process of drug-loaded microspheres is observed using confocal laser scanning microscopy and up-conversion luminescence microscopy. Meanwhile, the as-prepared NaYF(4):Yb(3+)/Er(3+)@SiO(2)@P(NIPAM-co-MAA) microspheres can be used as a luminescent probe for cell imaging. In addition, the extent of drug release can be monitored by the change of up-conversion emission intensity. These pH-induced thermally controlled drug release systems have potential to be used for in vivo bioimaging and cancer therapy by the pH of the microenvironment changing from 7.4 (normal physiological environment) to acidic microenvironments (such as endosome and lysosome compartments) owing to endocytosis.

Self-activated luminescent and mesoporous strontium hydroxyapatite nanorods for drug delivery

Multifunctional strontium hydroxyapatite (SrHAp) nanorods with luminescent and mesoporous properties have been successfully synthesized by a hydrothermal method. SEM and TEM images indicate that the mesoporous SrHAp samples consist of monodiperse nanorods with lengths of 120-150 nm, diameters of around 20 nm, and the mesopore size of 3-5 nm. The as-obtained SrHAp nanorods show an intense bright blue emission (centered at 432 nm, lifetime 11.6 ns, quantum efficiency: 22%), which might arise from CO(2)(*-) radical impurities in the crystal lattice under long-wavelength UV-light irradiation. Furthermore, the amount of trisodium citrate has an obvious impact on the particle size and the luminescence properties of the products, respectively. The drug storage/release test indicates that the luminescent SrHAp nanorods show a drug loading and controlled release properties for ibuprofen (IBU). Additionally, the emission intensity of SrHAp in the drug carrier system increases with the cumulative released amount of IBU, making the drug release might be easily tracked and monitored by the change of the luminescence intensity. This luminescent material may be potentially applied in the drug delivery and disease therapy fields.

Ln3+ (Ln = Eu, Dy, Sm, and Er) Ion-Doped YVO4 Nano/Microcrystals with Multiform Morphologies: Hydrothermal Synthesis, Growing Mechanism, and Luminescent Properties

YVO(4) nano/microcrystals with multiform morphologies, such as nanoparticles, microdoughnut, micropancake, pillar structure, and microflower, have been synthesized via a facile hydrothermal route. A series of controlled experiments indicate that the shape and size of as-prepared architectures can be tuned effectively by controlling the reaction conditions, such as reaction time, vanadium sources, different organic additives, and the molar ratio of organic additive trisodium citrate (Cit(3-)):Y(3+). It is found that Cit(3-) as a ligand and shape modifier has the dynamic effect by adjusting the growth rate of different facets under different experimental conditions, resulting in the formation of various geometries of the final products. The possible formation mechanisms for products with diverse architectures have been presented in detail. Additionally, we systematically investigate the luminescent properties of the YVO(4):Ln(3+) (Ln = Eu, Dy, Sm, and Er). Because of an efficient energy transfer from vanadate groups to dopants, YVO(4):Ln(3+) (Ln = Eu, Dy, Sm, and Er) phosphors showed their strong characteristic emission under ultraviolet excitation and low-voltage electron beam excitation. The ability to generate YVO(4) nano/microstructures with diverse shapes, multicolor emission, and higher quantum efficiency provides a great opportunity for systematically evaluating their luminescence properties, as well as fully exploring their applications in many types of color display fields.

UV-Emitting Upconversion-Based TiO2 Photosensitizing Nanoplatform: Near-Infrared Light Mediated in Vivo Photodynamic Therapy via Mitochondria-Involved Apoptosis Pathway

Photodynamic therapy (PDT) is a promising antitumor treatment that is based on the photosensitizers that inhibit cancer cells by yielding reactive oxygen species (ROS) after irradiation of light with specific wavelengths. As a potential photosensitizer, titanium dioxide (TiO2) exhibits minimal dark cytotoxicity and excellent ultraviolet (UV) light triggered cytotoxicity, but is challenged by the limited tissue penetration of UV light. Herein, a novel near-infrared (NIR) light activated photosensitizer for PDT based on TiO2-coated upconversion nanoparticle (UCNP) core/shell nanocomposites (UCNPs@TiO2 NCs) is designed. NaYF4:Yb(3+),Tm(3+)@NaGdF4:Yb(3+) core/shell UCNPs can efficiently convert NIR light to UV emission that matches well with the absorption of TiO2 shells. The UCNPs@TiO2 NCs endocytosed by cancer cells are able to generate intracellular ROS under NIR irradiation, decreasing the mitochondrial membrane potential to release cytochrome c into the cytosol and then activating caspase 3 to induce cancer cell apoptosis. NIR light triggered PDT of tumor-bearing mice with UCNPs@TiO2 as photosensitizers can suppress tumor growth efficiently due to the better tissue penetration than UV irradiation. On the basis of the evidence of in vitro and in vivo results, UCNPs@TiO2 NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy.

Monodisperse core–shell structured up-conversion Yb(OH)CO3@YbPO4:Er3+ hollow spheres as drug carriers

In this work, we report a facile solution-phase synthesis of monodisperse core-shell structured Yb(OH)CO₃@YbPO₄ hollow spheres (size around 380 nm) by utilizing the colloidal sphere of Yb(OH)CO₃ as the sacrificial template via the Kirkendall effect. The Er³+ doped Yb(OH)CO₃@YbPO₄ core-shell hollow spheres can be prepared similarly, which exhibit strong green emission under 980 nm NIR laser excitation even after loading with drug molecules. Most importantly, the sample can be used as an effective drug delivery carrier. The biocompatibility test on L929 fibroblast cells using MTT assay reveals low cytotoxicity of the system. A typical anticancer drug, doxorubicin hydrochloride (DOX), is used for drug loading, and the release properties, cytotoxicity, uptake behavior and therapeutic effects were examined. It is found that DOX is shuttled into cell by core-shell hollow spheres carrier and released inside cells after endocytosis, and the DOX-loaded spheres exhibited greater cytotoxicity than free DOX. These results indicate that the core-shell Er³+ doped Yb(OH)CO₃@YbPO₄ hollow spheres have potential for drug loading and delivery into cancer cells to induce cell death.

One-dimensional CaWO4 and CaWO4:Tb3+ nanowires and nanotubes: electrospinning preparation and luminescent properties

One-dimensional CaWO4 and CaWO4:Tb3+ nanowires and nanotubes have been prepared by a combination method of sol-gel process and electrospinning. X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), photoluminescence (PL), low voltage cathodoluminescence (CL) and time-resolved emission spectra, as well as kinetic decays were used to characterize the resulting samples. The results of XRD, FT-IR, TG-DTA indicate that the CaWO4 and CaWO4:Tb3+ samples begin to crystallize at 500 °C with the scheelite structure. Under ultraviolet excitation and low-voltage electron beams excitation, the CaWO4 samples exhibit a blue emission band with a maximum at 416 nm originating from the WO42−groups, while the CaWO4:Tb3+ samples show the characteristic emission of Tb3+ corresponding to 5D4–7F6,5,4,3 transitions due to an efficient energy transfer from WO42− to Tb3+. The energy transfer process was further studied by the time-resolved emission spectra as well as kinetic decay curves of Tb3+ upon excitation into the WO42−groups. Furthermore, the PL emission colour of CaWO4: x mol %Tb3+ can be tuned from blue to green by changing the concentrations (x) of the Tb3+ ion, making the materials have potential applications as fluorescent lamps and field emission displays (FEDs).

Doxorubicin conjugated NaYF4:Yb3+/Tm3+ nanoparticles for therapy and sensing of drug delivery by luminescence resonance energy transfer

In this study, we report an anticancer drug delivery system based on doxorubicin (DOX)-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles. The as-synthesized nanoparticles consist of uniform spherical nanoparticles with an average diameter of 25 nm. The drug delivery system demonstrates the ability to release DOX by cleavage of the hydrazone bond in mildly acidic environments. The spectra overlap between emission of donor NaYF(4):Yb(3+)/Tm(3+) nanoparticles at 452 nm ((1)D(2)→(3)F(4)) and 477 nm ((1)G(4)→(3)H(6)) and the broad absorbance of acceptor DOX centered at around 480 nm enables energy transfer to occur between the nanoparticles and DOX. The quenching and recovery of the up-conversion luminescence of NaYF(4):Yb(3+)/Tm(3+) by DOX due to luminescence resonance energy transfer (LRET) mechanism are applied as optical probe to confirm the DOX conjunction and monitor the release of DOX. The DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells via MTT assay. Meanwhile, the endocytosis process of DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles by SKVO3 cells was demonstrated through confocal laser scanning microscopy (CLSM), flow cytometry and ICP-OES. Such drug delivery system, which combines pH-triggered drug-release and up-converting nanoparticles-based LRET property, has excellent potential applications in cancer therapy and smart imaging.

Fabrication and Luminescence Properties of One-Dimensional CaMoO4: Ln3+ (Ln = Eu, Tb, Dy) Nanofibers via Electrospinning Process

One-dimensional CaMoO(4):Ln(3+) (Ln = Eu, Tb, Dy) nanofibers have been prepared by a combination method of sol-gel and electrospinning process. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and low voltage cathodoluminescence (CL) as well as kinetic decays were used to characterize the resulting samples. SEM and TEM analyses indicate that the obtained precursor fibers have a uniform size, and the as-formed CaMoO(4):Ln(3+) nanofibers consist of nanoparticles. Under ultraviolet excitation, the CaMoO(4) samples exhibit a blue-green emission band with a maximum at 500 nm originating from the MoO(4)(2-) groups. Due to an efficient energy transfer from molybdate groups to dopants, CaMoO(4):Ln(3+) phosphors show their strong characteristic emission under ultraviolet excitation and low-voltage electron beam excitation. The energy transfer process was further studied by the emission spectra and the kinetic decay curves of Ln(3+) upon excitation into the MoO(4)(2-) groups in the CaMoO(4):x mol % Ln(3+) samples (x = 0-5). Furthermore, the emission colors of CaMoO(4):Ln(3+) nanofibers can be tuned from blue-green to green, yellow, and orange-red easily by changing the doping concentrations (x) of Ln(3+) ions, making the materials have potential applications in fluorescent lamps and field emission displays (FEDs).

One-dimensional luminescent materials derived from the electrospinning process: preparation, characteristics and application

This feature article highlights the recent advances on the preparation, characteristics and application of one-dimensional (1D) luminescent materials (including rare earth based inorganic materials, rare earth based composite materials and non rare earth materials) by an electrospinning process. Electrospinning is an effective method to prepare 1D polymer, composite and inorganic submicro- or nano-materials. The key strategy of the electrospinning method is to form an electrospinning solution with viscoelastic behavior similar to that of a conventional polymer solution. It utilizes an electrical force on the surface of an electrospinning solution to overcome the surface tension and produce a very thin charged jet. This jet moves straight for a certain distance, and then bends into looping and spiraling paths. During the elongation of the liquid jet, solvent evaporates and 1D hybrid materials accumulate on a grounded collector. Dispersing complexes or inorganic nanoparticles into polymer and inorganic matrices, composite luminescent materials viaelectrospinning combine both inorganic and organic characters. Annealing the inorganic/polymer hybrid precursors can yield various kinds of inorganic luminescent materials with fiber, wire, belt and tube-like morphologies, which have potential applications in fluorescent lamps and color displays. Furthermore, with the addition of some surfactants, it is possible to prepare 1D luminescent and porous multifunctional materials, which can act as potential drug carriers in the biomedical area.