Xiaopeng Zheng

High-Throughput Synthesis of Single-Layer MoS2 Nanosheets as a Near-Infrared Photothermal-Triggered Drug Delivery for Effective Cancer Therapy

We report here a simple, high-yield yet low-cost approach to design single-layer MoS2 nanosheets with controllable size via an improved oleum treatment exfoliation process. By decorating MoS2 nanosheets with chitosan, these functionalized MoS2 nanosheets have been developed as a chemotherapeutic drug nanocarrier for near-infrared (NIR) photothermal-triggered drug delivery, facilitating the combination of chemotherapy and photothermal therapy into one system for cancer therapy. Loaded doxorubicin could be controllably released upon the photothermal effect induced by 808 nm NIR laser irradiation. In vitro and in vivo tumor ablation studies demonstrate a better synergistic therapeutic effect of the combined treatment, compared with either chemotherapy or photothermal therapy alone. Finally, MoS2 nanosheets can also be used as a promising contrast agent in X-ray computed tomography imaging due to the obvious X-ray absorption ability of Mo. As a result, the high-throughput oleum treatment exfoliation process could be extended for fabricating other 2D nanomaterials, and the NIR-triggered drug release strategy was encouraging for simultaneous imaging-guided cancer theranostic application.

TPGS-stabilized NaYbF4:Er upconversion nanoparticles for dual-modal fluorescent/CT imaging and anticancer drug delivery to overcome multi-drug resistance

Multi-drug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively investigated for overcoming MDR in cancer therapy because of its ability to inhibit P-glycoprotein (P-gp). In this work, TPGS was for the first time used as a new surface modifier to functionalize NaYbF4:Er upconversion nanoparticles (UNCPs) and endowed the as-prepared products (TPGS-UCNPs) with excellent water-solubility, P-gp inhibition capability and imaging-guided drug delivery property. After the chemotherapeutic drug (doxorubicin, DOX) loading, the as-formed composites (TPGS-UCNPs-DOX) exhibited potent killing ability for DOX-resistant MCF-7 cells. Flow-cytometric assessment and Western blot assay showed that the TPGS-UCNPs could potently decrease the P-gp expression and facilitate the intracellular drug accumulation, thus achieving MDR reversal. Moreover, considering that UCNPs process efficient upconversion emission and Yb element contained in UCNPs has strong X-ray attenuation ability, the as-obtained composite could also serve as a dual-modal probe for upconversion luminescence (UCL) imaging and X-ray computed tomography (CT) imaging, making them promising for imaging-guided cancer therapy.

Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat and Fe3O4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS2/Fe3O4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo. Specifically, the MSIOs can be applied as a dual-modal probe for T2-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.

Mesoporous NaYbF4@NaGdF4 core-shell up-conversion nanoparticles for targeted drug delivery and multimodal imaging

We developed a facile strategy to obtain a new kind of mesoporous core-shell structured up-conversion nanoparticles (mUCNPs), composed of a NaYbF4:2%Er core and a mesoporous NaGdF4 shell. This mesoporous shell not only enhanced the up-conversion luminescence but also endowed many other functionalities of the nanoparticles such as drug delivery and bio-imaging capabilities. Moreover, after being conjugated with polyethylenimine (PEI) and folic acid (FA), core-shell mUCNPs exhibited good water dispersibility, enhanced drug delivery efficiency, and remarkable targeting ability to cancer cells. To certify the folate receptors (FR)-mediated targeted drug delivery, cell viability assay, cell up-conversion luminescence imaging and flow cytometry analysis were carried out. Furthermore, apart from the application for targeted drug delivery, the as-prepared core-shell mUCNPs could also be employed as the contrast agents for X-ray computed tomography (CT) and magnetic resonance (MR) imaging, because of the strong X-ray attenuation ability of Yb and high longitudinal molar relaxivity (r1) of Gd in the nanoparticles, providing the potential for simultaneously bio-imaging and cancer-targeting therapy.

Multifunctional Rbx WO3 nanorods for simultaneous combined chemo-photothermal therapy and photoacoustic/CT imaging.

Light-triggered drug delivery based on near-infrared (NIR)-mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light-responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light-absorber, Rb(x) WO3 (rubidium tungsten bronze, Rb-TB) nanorods. With doxorubicin (DOX) payload, the DOX-loaded Rb-TB composite (Rb-TB-DOX) simultaneously provides a burst-like drug release and intense heating effect upon 808-nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb-TB-DOX to the MCF-7 cancer cells. Most remarkably, Rb-TB-DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX-resistant MCF-7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo-photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo-photothermal therapy is also conducted and realized on pancreatic (Pance-1) tumor-bearing nude mice. Apart from its promise for cancer therapy, the as-prepared Rb-TB can also be employed as a new dual-modal contrast agent for photoacoustic tomography and (PAT) X-ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X-ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb(x)WO3 nanorods for applications in cancer theranostics.

Phytotoxicity, Translocation, and Biotransformation of NaYF4 Upconversion Nanoparticles in a Soybean Plant

The increasing uses of rare-earth-doped upconversion nanoparticles (UCNPs) have obviously caused many concerns about their potential toxicology on live organisms. In addition, the UCNPs can be released into the environment, then transported into edible crop plants, and finally entered into food chain. Here, the soybean is chosen as a model plant to study the subchronic phytotoxicity, translocation, and biotransformation of NaYF4 UCNPs. The incubation with UCNPs at a relative low concentration of 10 μg mL(-1) leads to growth promotion for the roots and stems, while concentration exceeding 50 μg mL(-1) brings concentration-dependent inhibition. Upconversion luminescence imaging and scanning electron microscope characterization show that the UCNPs can be absorbed by roots and parts of the adsorbed UCNPs are then transported through vessels to stems and leaves. The near-edge X-ray absorption fine structure spectra reveal that the adsorbed NaYF4 nanoparticles are relatively stable during a 10 d incubation. Energy-dispersive X-ray spectrum further indicates that a small amount of NaYF4 is dissolved/digested and can transform into Y-phosphate clusters in roots.

Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract.

Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile solvothermal method and then coated with a SiO2 layer to improve their biocompatibility and stability in the harsh environments of the GI tract, such as the stomach and the small intestine. Due to their strong X-ray- and near infrared-absorption abilities, we demonstrate that, following oral administration in mice, the Bi2S3@SiO2 NRs can be used as a dual-modal contrast agent for the real-time and non-invasive visualization of NRs distribution and the GI tract via both X-ray computed tomography (CT) and photoacoustic tomography (PAT) techniques. Importantly, integration of PAT with CT provides complementary information on anatomical details with high spatial resolution. In addition, we use Caenorhabditis Elegans (C. Elegans) as a simple model organism to investigate the biological response of Bi2S3@SiO2 NRs by oral administration. The results indicate that these NRs can pass through the GI tract of C. Elegans without inducing notable toxicological effects. The above results suggest that Bi2S3@SiO2 NRs pave an alternative way for the fabrication of multi-modal contrast agents which integrate CT and PAT modalities for a direct and non-invasive visualization of the GI tract with low toxicity.

One-Pot Template-Free Synthesis of NaYF4 Upconversion Hollow Nanospheres for Bioimaging and Drug Delivery

Hollow-structured nanomaterials with fluorescent properties are extremely attractive for image-guided cancer therapy. In this paper, sub-100 nm and hydrophilic NaYF4 upconversion (UC) hollow nanospheres (HNSs) with multicolor UC luminescence and drug-delivery properties were successfully prepared by a facile one-pot template-free hydrothermal route using polyetherimide (PEI) polymer as the stabilizing agent. XRD, SEM, TEM, and N2-adsorption/desorption were used to characterize the as-obtained products. The growth mechanism of the HNSs has been systematically investigated on the basis of the Ostwald ripening. Under 980 nm excitation, UC emissions of HNSs can be tuned by a simple change of the concentration or combination of various upconverters. As a result, the PEI-coated HNSs could be used as efficient probes for in vitro upconversion luminescence (UCL) cell imaging. Furthermore, a doxorubicin storage/release behavior and cancer-cell-killing ability investigation reveal that the product has the potential to be a drug carrier for cancer therapy.

Er3+-doped YbPO4 up-conversion porous nanospheres for UCL/CT bimodal imaging in vivo and chemotherapy

The combined use nanotechnology and medical technologies holds great promise for the development and improvement of various theranostic media. Here, based on a facile hydrothermal method, polyethyleneimine (PEI) functionalized YbPO4:Er up-conversion porous nanospheres (UCPSs) were fabricated, which combined the capabilities of up-conversion luminescence (UCL)/X-ray computed tomography (CT) bimodal imaging and drug delivery. The resulting hydrophilic PEI functionalized YbPO4:Er UCPSs (PEI-UCPSs) showed uniform morphology and high crystallinity. Moreover, PEI-UCPSs possessed high drug loading capacity because of their large specific surface area, which was confirmed by the Brunauer-Emmett-Teller (BET) experiment. Cellular experiments indicated that the PEI-UCPSs had low cytotoxicity and confirmed the performance of the pH-mediated cancer targeting of PEI-UCPSs@DOX. Importantly, because of the ideal UCL property and high CT contrast both in vitro and in vivo, YbPO4:Er PEI-UCPSs could be used as an optical probe and a contrast agent for optical and CT imaging, forming a promising platform for simultaneous bioimaging and drug delivery.