Xinghua Dong

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.

One-pot synthesis of PEGylated plasmonic MoO3–x hollow nanospheres for photoacoustic imaging guided chemo-photothermal combinational therapy of cancer

Engineering design of plasmonic nanomaterials as on-demand theranostic nanoagents with imaging, drug carrier, and photothermal therapy (PTT) functions have profound impact on treatment of cancer. Here, a facile one-pot template-free hydrothermal route was firstly developed for synthesis of plasmonic oxygen deficiency molybdenum oxide hollow nanospheres functionalized by poly(ethylene glycol) (PEG-MoO(3-x) HNSs). The as-prepared PEG-MoO(3-x) HNSs not only have good biocompatibility but also exhibit obvious localized surface plasmon resonance (LSPR) absorption in the near-infrared (NIR) region. Especially, due to its intrinsic mesoporous properties and effective photothermal conversion efficiency upon 808-nm NIR laser irradiation, the PEG-MoO(3-x) HNSs can be applied as a pH/NIR laser dual-responsive camptothecin (CPT) drug delivery nanoplatform for chemotherapy as well as PTT to cancer cells. A remarkably improved synergistic therapeutic effect to pancreatic (PANC-1) tumor-bearing mice was obtained compared to the result of chemotherapy or PTT alone. Apart from its application for drug delivery, the PEG-MoO(3-x) HNSs can also be employed as an effective contrast nanoagent for photoacoustic (PAT) imaging because of its high NIR absorption, making it promising as a theranostic nanoagent for PAT imaging-guided chemo-photothermal combinational cancer therapy in the nanomedicine field.

Polyoxometalate-Based Radiosensitization Platform for Treating Hypoxic Tumors by Attenuating Radioresistance and Enhancing Radiation Response

Radioresistance is one of the undesirable impediments in hypoxic tumors, which sharply diminishes the therapeutic effectiveness of radiotherapy and eventually results in the failure of their treatments. An attractive strategy for attenuating radioresistance is developing an ideal radiosensitization system with appreciable radiosensitization capacity to attenuate tumor hypoxia and reinforce radiotherapy response in hypoxic tumors. Therefore, we describe the development of Gd-containing polyoxometalates-conjugated chitosan (GdW10@CS nanosphere) as a radiosensitization system for simultaneous extrinsic and intrinsic radiosensitization, by generating an overabundance of cytotoxic reactive oxygen species (ROS) using high-energy X-ray stimulation and mediating the hypoxia-inducible factor-1a (HIF-1a) siRNA to down-regulate HIF-1α expression and suppress broken double-stranded DNA self-healing. Most importantly, the GdW10@CS nanospheres have the capacity to promote the exhaustion of intracellular glutathione (reduced GSH) by synergy W6+-triggered GSH oxidation for sufficient ROS generation, thereby facilitating the therapeutic efficiency of radiotherapy. As a result, the as-synthesized GdW10@CS nanosphere can overcome radioresistance of hypoxic tumors through a simultaneous extrinsic and intrinsic strategy to improve radiosensitivity. We have demonstrated GdW10@CS nanospheres with special radiosensitization behavior, which provides a versatile approach to solve the critical radioresistance issue of hypoxic tumors.

Synthesis of BSA-Coated BiOI@Bi2S3 Semiconductor Heterojunction Nanoparticles and Their Applications for Radio/Photodynamic/Photothermal Synergistic Therapy of Tumor

Developing an effective theranostic nanoplatform remains a great challenge for cancer diagnosis and treatment. Here, BiOI@Bi2 S3 @BSA (bovine serum albumin) semiconductor heterojunction nanoparticles (SHNPs) for triple-combination radio/photodynamic/photothermal cancer therapy and multimodal computed tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs possess strong X-ray attenuation capability since they contain high-Z elements, and thus they are anticipated to be a very competent candidate as radio-sensitizing materials for radiotherapy enhancement. On the other hand, as a semiconductor, the as-prepared SHNPs offer an extra approach for reactive oxygen species generation based on electron-hole pair under the irradiation of X-ray through the photodynamic therapy process. This X-ray excited photodynamic therapy obviously has better penetration depth in bio-tissue. Whats more, the SHNPs also possess well photothermal conversion efficiency for photothermal therapy, because Bi2 S3 is a thin band semiconductor with strong near-infrared absorption that can cause local overheat. In vivo tumor ablation studies show that synergistic radio/photodynamic/photothermal therapy achieves more significant therapeutic effect than any single treatment. In addition, with the strong X-ray attenuation and high near-infrared absorption, the as-obtained SHNPs can also be applied as a multimodal contrast agent in CT/PA imaging.

Multifunctional WS2@Polyetherimide Nanoplatforms for Imaging Guided Gene‐Photothermal Synergistic Therapy of Cancer

The combination of photothermal therapy (PTT) with gene therapy (GT) to improve PTT efficiency and thus eliminate cancer cells under mild hyperthermia is highly needed. Herein, multifunctional WS2 @poly(ethylene imine) (WS2 @PEI) nanoplatform has been designed and constructed for gene-photothermal synergistic therapy of tumors at mild condition. After a surface modification of WS2 with a positively charged PEI, the as-prepared WS2 @PEI nanoplatform can not only act as an efficient survivin-siRNA carrier for GT but also exhibit remarkable near-infrared (NIR) photothermal effects for PTT. On the one hand, the photothermal effects induced by WS2 @PEI upon NIR irradiation can enhance the cellular uptake owing to the increase of the cell membrane permeability, which leads to the remarkable enhancement of silencing efficiency of survivin. On the other hand, the silencing of survivin can increase the apoptosis as well as reduce the heat resistance of cancer cells by downregulating the heat shock protein 70 expressions, which greatly enhance the sensitivity of cancer cells to PTT. As a result, compared to PTT or GT treatment alone, WS2 @PEI mediated synergistic GT/PTT therapy remarkably enhances in vitro cancer cell damage and in vivo tumor elimination.

Mesoporous Bamboo Charcoal Nanoparticles as a New Near-Infrared Responsive Drug Carrier for Imaging-Guided Chemotherapy/Photothermal Synergistic Therapy of Tumor.

Near-infrared-(NIR)-light-triggered photothermal nanocarriers have attracted much attention for the construction of more smart and effective therapeutic platforms in nanomedicine. Here, a multifunctional drug carrier based on a low cost, natural, and biocompatible material, bamboo charcoal nanoparticles (BCNPs), which are prepared by the pyrolysis of bamboo followed by physical grinding and ultrasonication is reported. The as-prepared BCNPs with porous structure possess not only large surface areas for drug loading but also an efficient photothermal effect, making them become both a suitable drug carrier and photothermal agent for cancer therapy. After loading doxorubicin (DOX) into the BCNPs, the resulting DOX-BCNPs enhance drug potency and more importantly can overcome the drug resistance of DOX in a MCF-7 cancer cell model by significantly increasing cellular uptake while remarkably decreasing drug efflux. The in vivo synergistic effect of combining chemotherapy and photothermal therapy in this drug delivery system is also demonstrated. In addition, the BCNPs enhance optoacoustic imaging contrast due to their high NIR absorbance. Collectively, it is demonstrated that the BCNP drug delivery system constitutes a promising and effective nanocarrier for simultaneous bioimaging and chemo-photothermal synergistic therapy of cancer.

Fluorescent supramolecular micelles for imaging-guided cancer therapy

A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.

Therapeutic Nanoparticles Based on Curcumin and Bamboo Charcoal Nanoparticles for Chemo-Photothermal Synergistic Treatment of Cancer and Radioprotection of Normal Cells

Low water solubility, extensive metabolism, and drug resistance are the existing unavoidable disadvantages of the insoluble drug curcumin in biomedical applications. Herein, we employed d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-functionalized near-infrared (NIR)-triggered photothermal mesoporous nanocarriers with bamboo charcoal nanoparticles (TPGS-BCNPs) to load and deliver curcumin for improving its bioavailability. This system could considerably increase the accumulation of curcumin in cancer cells for enhanced curcumin bioavailability via simultaneously promoting the cellular internalization of the as-synthesized composite (TPGS-BCNPs@curcumin) by the size effect of NPs and considerably triggering controlled curcumin release from TPGS-BCNPs@curcumin by NIR stimulation and reducing efflux of curcumin by the P-glycoprotein (P-gp) inhibition of TPGS, so as to enhance the therapeutic effect of curcumin and realize a better chemo-photothermal synergetic therapy in vitro and in vivo. Besides cancer therapy, studies indicated that curcumin and some carbon materials could be used as radical scavengers that play an important role in the radioprotection of normal cells. Hence, we also investigated the free-radical-scavenging ability of the TPGS-BCNPs@curcumin composite in vitro to preliminarily evaluate its radioprotection ability for healthy tissues. Therefore, our work provides a multifunctional delivery system for curcumin bioavailability enhancement, chemo-photothermal synergetic therapy of cancer, and radioprotection of healthy tissues.

Intelligent MoS2 Nanotheranostic for Targeted and Enzyme-/pH-/NIR-Responsive Drug Delivery To Overcome Cancer Chemotherapy Resistance Guided by PET Imaging

Chemotherapy resistance remains a major hurdle for cancer therapy in clinic because of the poor cellular uptake and insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS2 nanotheranostic (MoS2-PEI-HA) ingeniously decorated with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with the chemotherapy drug doxorubicin (DOX). HA can not only target CD44-overexpressing MCF-7-ADR but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment, thus accelerating DOX release. Furthermore, MoS2 with strong near-infrared (NIR) photothermal conversion ability can also promote the release of DOX in the acidic tumor environment at a mild 808 nm laser irradiation, achieving a superior antitumor activity based on the programmed response to HAase and NIR laser actuator. Most importantly, HA targeting combined with mild NIR laser stimuli, rather than using hyperthermia, can potently downregulate the expression of drug-resistance-related P-glycoprotein (P-gp), resulting in greatly enhanced intracellular drug accumulation, thus achieving drug resistance reversal. After labeled with 64Cu by a simple chelation strategy, MoS2 was employed for real-time positron emission tomography (PET) imaging of MCF-7-ADR tumor in vivo. This multifunctional nanoplatform paves a new avenue for PET imaging-guided spatial-temporal-controlled accurate therapy of drug-resistant cancer.

MoS2-Nanosheet-Assisted Coordination of Metal Ions with Porphyrin for Rapid Detection and Removal of Cadmium Ions in Aqueous Media

Molybdenum disulfide (MoS2) is a two-dimensional (2D) graphene-like material that is gaining great attention because of its potential application in various fields. Here, we reported a self-assembled nanocomposite consisted of MoS2 nanosheets and 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrintetra(p-toluenesulfonate) (TMPyP), named MoS2@TMPyP. This nanocomposite can be used as a sensing probe for low cost, rapid, selective detection of cadmium (Cd2+) ions. It is found that a new Soret band at 442 nm in UV-vis absorption spectra represented the coordination of Cd2+ ions into TMPyP of the MoS2@TMPyP. The coordination rates between TMPyP and Cd2+ ions is greatly accelerated from 72 h to 20 min with the assistance of MoS2, which is 200 times faster than in the absence of MoS2. The limit of detection (LOD) of the Cd2+ is as low as 7.2 × 10-8 mol/L. The binding behavior between the cationic TMPyP and MoS2 nanosheets was corroborated by molecular dynamics simulation and various control experiments. The results demonstrated that electrostatic interaction was the main force for driving TMPyP enriching around the MoS2 surface, resulting in an accelerated complexation of Cd2+ and TMPyP. Moreover, MoS2@TMPyP nanocomposite can also be used for removing of Cd2+ in water. The removal efficiency (RF) of the MoS2@TMPyP can reach to 91% for high concentrations of Cd2+. This work provides a new insight into detection and removal of Cd2+ ions in water.