Ruichan Lv

Highly Uniform Hollow GdF3 Spheres: Controllable Synthesis, Tuned Luminescence, and Drug-Release Properties

In this paper, uniform hollow mesoporous GdF3 micro/nanospheres were successfully prepared by a facile two-step synthesis route without using any surfactant, catalyst, and further calcination process. The precursor Gd(OH)CO3 spheres are prepared by a coprecipitation process. After that, uniform and size-tunable GdF3 hollow spheres were easily coprecipitated with NaBF4 at the sacrifice of the precursor with low temperature and short reaction time. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution TEM, N2 adsorption/desorption, and up-conversion (UC) photoluminescence spectra were used to characterize the as-obtained products. It is found that the initial pH value and NaBF4/Gd(3+) molar ratios play important roles in the structures, sizes, and phases of the hollow products. The growth mechanism of the hollow spheres has been systematically investigated based on the Kirkendall effect. Under 980 nm IR laser excitation, UC luminescence of the as-prepared Yb(3+)/Er(3+)-codoped GdF3 hollow spheres can be changed by a simple adjustment of the concentration of the Yb(3+) ion. Enhanced red emission is obtained by introducing Li(+) ions in GdF3:Yb(3+)/Er(3+). Furthermore, a doxorubicin release experiment and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay reveal that the product has potential application in drug delivery and targeted cancer therapy.

Au25 cluster functionalized metal–organic nanostructures for magnetically targeted photodynamic/photothermal therapy triggered by single wavelength 808 nm near-infrared light

Near-infrared (NIR) light-induced cancer therapy has gained considerable interest, but pure inorganic anti-cancer platforms usually suffer from degradation issues. Here, we designed metal-organic frameworks (MOFs) of Fe3O4/ZIF-8-Au25 (IZA) nanospheres through a green and economic procedure. The encapsulated Fe3O4 nanocrystals not only produce hyperthemal effects upon NIR light irradiation to effectively kill tumor cells, but also present targeting and MRI imaging capability. More importantly, the attached ultrasmall Au25(SR)18(-) clusters (about 2.5 nm) produce highly reactive singlet oxygen ((1)O2) to cause photodynamic effects through direct sensitization under NIR light irradiation. Furthermore, the Au25(SR)18(-) clusters also give a hand to the hyperthemal effect as photothermal fortifiers. This nanoplatform exhibits high biocompatibility and an enhanced synergistic therapeutic effect superior to any single therapy, as verified by in vitro and in vivo assay. This image-guided therapy based on a metal-organic framework may stimulate interest in developing other kinds of metal-organic materials with multifunctionality for tumor diagnosis and therapy.

Surfactant-Free Synthesis, Luminescent Properties, and Drug-Release Properties of LaF3 and LaCO3F Hollow Microspheres

Uniform LaF3 and LaCO3F hollow microspheres were successfully synthesized through a surfactant-free route by employing La(OH)CO3 colloidal microspheres as a sacrificial template and NaBF4 as the fluorine source. The synthetic process consists of two steps: the preparation of a La(OH)CO3 precursor via a facile urea-based precipitation and the following formation of lanthanide fluoride hollow microspheres under aqueous conditions at low temperature (50 °C) and short reaction time (3 h), without using any surfactant and catalyst. The formation of hollow spheres with controlled size can be assigned to the Kirkendall effect. It is found that the phase and structure of the products can be simply tuned by changing the pH values of the solution. Time-dependent experiments were employed to study the possible formation process. N2 adsorption/desorption results indicate the mesoporous nature of LaF3 hollow spheres. Yb(3+)/Er(3+) (Ho(3+)) and Yb(3+)/Tm(3+)-doped LaF3 hollow spheres exhibit characteristic up-conversion (UC) emissions of Er(3+) (Ho(3+)) and Tm(3+) under 980 nm laser-diode excitation, and Ce(3+)/Tb(3+)-doped LaF3 and LaCO3F emit bright yellow-green and near-white light under UV irradiation, respectively. In particular, LaF3:Yb/Er and LaCO3F:Ce/Tb hollow microspheres exhibit obvious sustained and pH-dependent doxorubicin release properties. The luminescent properties of the carriers allow them to be tracked or monitored during the release or therapy process, suggesting their high potential in the biomedical field.

Multifunctional SiO2@Gd2O3:Yb/Tm hollow capsules: controllable synthesis and drug release properties.

A series of hollow and luminescent capsules have been fabricated by covering luminescent Gd2O3:Yb/Tm nanoparticles on the surface of uniform hollow mesoporous silica capsules (HMSCs), which were obtained from an etching process using Fe3O4 as hard templates. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), up-conversion (UC) fluorescence spectra, and N2 adsorption-desorption were used to characterize these samples. It is found that the as-prepared products have mesoporous pores, large specific surface, and high dispersity. In particular, the size, shape, surface area, and interior space of the composites can be finely tuned by adjusting the size and morphology of the magnetic cores. Under 980 nm near-infrared (NIR) laser irradiation, the composites show characteristic blue UC emissions of Tm(3+) even after carrying doxorubicin hydrochloride (DOX). The drug-release test reveals that the capsules showed an apparent sustained release character and released in a pH-sensitive manner. Interestingly, the UC luminescence intensity of the drug-carrying system increases with the released DOX, realizing the possibility to track or monitor the released drug by the change of UC fluorescence simultaneously, which should be highly promising in anticancer drug delivery and targeted cancer therapy.

Charge convertibility and near infrared photon co-enhanced cisplatin chemotherapy based on upconversion nanoplatform

Optimal nano-sized drug carrier requires long blood circulation, selective extravasation, and efficient cell uptake. Here we develop a charge-convertible nanoplatform based on Pt(IV) prodrug loaded NaYF4:Yb,Tm upconversion nanoparticles (UCNs), followed by coating a layer of PEG-PAH-DMMA polymer (UCNs-Pt(IV)@PEG-PAH-DMMA). The polymer endows the platform with high biocompatibility, initial nano-size for prolonged blood circulation and selective extravasation. Especially, the anionic polymer can response to the mild acidic stimulus (pH ∼6.5) of tumor extracellular microenvironment and experience charge-shifting to a cationic polymer, resulting in electrostatic repulsion and releases of positive UCNs-Pt(IV). The positive UCNs-Pt(IV) nanoparticles have high affinity to negative cell membrane, leading to efficacious cell internalization. Simultaneously, the ultraviolet (UV) light emitted from UCNs upon near-infrared (NIR) light irradiation, together with the reductive glutathione (GSH) in cancer cells efficiently activate the Pt(IV) prodrug to highly cytotoxic Pt(II), realizing NIR photon improved chemotherapy. The experimental results reveal the charge convertibility, low adverse effect and markedly enhanced tumor ablation efficacy upon NIR laser irradiation of this smart nanoplatform. Moreover, combining the inherent upconversion luminescence (UCL) and computed tomography (CT) imaging capabilities, an alliance of cancer diagnosis and therapy has been achieved.

CuS–Pt(IV)–PEG–FA nanoparticles for targeted photothermal and chemotherapy

Platinum (Pt)(iv) pro-drugs, which can be reduced to highly cytotoxic Pt(ii) by high concentrations of glutathione (GSH) in cancer cells, offer a new approach to defense against tumors. A carrier with controlled release and targeted functions is essential to determine its final anticancer efficiency. In this study, we report a targeted drug delivery system by fabricating CuS-Pt(iv)-PEG-FA nanoparticles (CuS-Pt(iv) NPs) that integrates Pt drug-induced chemotherapy and CuS nanoparticles-mediated photothermal therapy (PTT) under near infrared (NIR) light irradiation. The attached PEG and folic acid (FA) molecules endow the system with high biocompatibility and targeted property. The release of Pt was up to 84.4% in the presence of GSH in the tumor cells due to the reduction property of GSH. Combined with the photothermal effect with high photothermal conversion efficiency (32.1%) upon NIR light irradiation, a remarkable tumor inhabitation efficacy was been achieved. The in vitro assay manifested that CuS-Pt(iv) NPs can kill more cancer cells than that of DSP and cisplatin; the in vivo results indicate that the group treated with intravenous injection of CuS-Pt(iv) NPs exhibits excellent antitumor effects upon NIR light irradiation.

UCNPs@gelatin–ZnPc nanocomposite: synthesis, imaging and anticancer properties

To enhance the total emission intensity, particularly the red emission of Yb,Er co-doped nanoparticles for red light activated photodynamic therapy (PDT), we doped Mn2+ ions into the NaGdF4:Yb,Er core, and subsequently coated the NaGdF4:Yb active shell to fabricate core-shell structured, up-conversion nanoparticles of NaGdF4:Yb,Er,Mn@NaGdF4:Yb (abbreviated as UCNPs). A novel and facile encapsulation method with gelatin has been proposed to transfer oleic acid (OA) stabilized UCNPs into an aqueous solution and simultaneously decorate zinc phthalocyanine (ZnPc) photosensitizer molecules. In the encapsulation process, ZnPc molecules are wrapped in the interlaced net structure of the peptide chain from gelatin, forming the UCNPs@gel-ZnPc nanocomposite. The nanoplatform has high emission intensity and excellent biocompatibility, as was expected. More importantly, the enhanced red emission of UCNPs has significant overlap with the UV absorbance of ZnPc; therefore, it can effectively activate the sensitizer to produce a large amount of singlet oxygen reactive oxygen species (ROS, 1O2) to kill cancer cells, which has evidently been verified by the in vitro results. Combined with the inherent up-conversion luminescence (UCL) imaging properties, this UCNPs@gel-ZnPc nanoplatform could have potential application in PDT and imaging fields.

Design, fabrication, luminescence and biomedical applications of UCNPs@mSiO2–ZnPc–CDs–P(NIPAm-MAA) nanocomposites

A nanoplatform capable of pH/thermo-coupling sensitive drug release, multimodal imaging, and synergetic antitumor therapy was designed and prepared. The core-shell structured platform consists of a dominant red up-converted luminescence (UCL) core and a copolymer P(NIPAm-MAA) gated mesoporous silica layer with functional cargos loaded inside. Due to the tri-doped Yb/Ce/Ho ions in the core and the inert shell coating, the nanoparticles show intense red UCL under NIR laser excitation. Thereafter, the emitted red light transfers energy to the conjugated photodynamic therapy (PDT) agent zinc(ii)-phthalocyanine (ZnPc), which produces singlet oxygen, and the decorated carbon dots (CDs) generate an obvious photothermal effect upon 980 nm laser irradiation as well as avoiding ZnPc leakage. Notably, the thermal effect together with the acidic environment in the cancer sites induces the shrinkage of P(NIPAm-MAA), realizing targeted and controllable release of DOX. Due to the photothermal-/photodynamic-/chemo-therapy derived synergistic effect, the nanoplatform exhibits desirable tumor inhibition efficacy, as verified by both in vitro and in vivo results. In particular, the doped rare earth ions enable the product to have simultaneous UCL, magnetic resonance imaging (MRI) and computed tomography (CT) imaging properties, thus achieving the integration of diagnosis and therapy.

A Versatile Near Infrared Light Triggered Dual-Photosensitizer for Synchronous Bioimaging and Photodynamic Therapy

Photodynamic therapy (PDT) based on Tm3+-activated up-conversion nanoparticles (UCNPs) can effectively eliminate tumor cells by triggering inorganic photosensitizers to generate cytotoxic reactive oxygen species (ROS) upon tissue penetrating near-infrared (NIR) light irradiation. However, the partial use of the emitted lights from UCNPs greatly hinders their application. Here we develop a novel dual-photosensitizer nanoplatform by coating mesoporous graphitic-phase carbon nitride (g-C3N4) layer on UCNPs core, followed by attaching ultrasmall Au25 nanoclusters and PEG molecules (named as UCNPs@g-C3N4-Au25-PEG). The ultraviolet-visible (UV-vis) light and the intensive near infrared (NIR) emission from UCNPs can activate g-C3N4 and excite Au25 nanoclusters to produce ROS, respectively, and thus realize the simultaneous activation of two kinds of photosensitizers for enhanced the efficiency of PDT mediated by a single NIR light excitation. A markedly higher PDT efficacy for the dual-photosensitizer system than any single modality has been verified by the enhanced ROS production and in vitro and in vivo results. By combining the inherent multi-imaging properties (up-conversion, CT, and MRI) of UCNPs, an imaging guided therapeutic platform has been built. As the first report of dual-inorganic-photosensitizer PDT agent, our developed system may be of high potential in future NIR light induced PDT application.

Mesoporous NaYF4:Yb,Er@Au–Pt(IV)-FA nanospheres for dual-modal imaging and synergistic photothermal/chemo-anti-cancer therapy

In this report, mesoporous NaYF4:Yb,Er@Au–Pt(IV)-FA up-conversion nanoparticles (UCNPs) have been designed by attaching Au NPs and Pt(IV) pro-drugs on the surface of PEI hydrogel modified mesoporous NaYF4:Yb,Er nanospheres. Finally the molecules modified with folic acid (FA) improve the receptor-mediated endocytosis. Because of the doped rare earth ions in the host matrix, the as-synthesized platform exhibits excellent up-conversion luminescence (UCL) imaging and computed X-ray tomography (CT) imaging properties. Diverse methods including MTT assay, hemolysis experiments, and live/dead cell analysis were employed to evaluate the biocompatibility and ablation efficacy of the as-synthesized platform. It was found that the cytotoxicity of the platform can be tuned by eliminating the axial ligands reductively during intracellular endocytosis. Especially, under 980 nm near-infrared (NIR) irradiation, the platform shows excellent inhibition toward cancer cells due to the synergistic photothermal injury to enzymes and membrane integrity combined with the DNA binding of activated Pt(II) to avoid cell proliferation. The developed nanocomposite may thus be a promising imaging-guided synergistic anti-cancer platform.