Da Huo

Synthesis and application of strawberry-like Fe3O4-Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease

Development of non-invasive assay for the accurate diagnosis of progressive liver diseases (e.g., fatty liver and hepatocellular carcinoma (HCC)) is of great clinical significance and remains to be a big challenge. Herein, we reported the synthesis of strawberry-like Fe3O4-Au hybrid nanoparticles at room temperature that simultaneously exhibited fluorescence, enhanced X-ray attenuation, and magnetic properties. The results of in vitro fluorescence assay showed that the nanoparticles had significant photo-stability and could avoid the endosome degradation in cells. The in vivo imaging of normal mice demonstrated that the Fe3O4-Au nanoparticles provided 34.61-fold contrast enhancement under magnetic resonance (MR) guidance 15 min post the administration. Computed tomography (CT) measurements showed that the highest Hounsfield Unit (HU) was 174 at 30 min post the injection of Fe3O4-Au nanoparticles. In vivo performance of the Fe3O4-Au nanoparticles was further evaluated in rat models bearing three different liver diseases. For the fatty liver model, nearly homogeneous contrast enhancement was observed under both MR (highest contrast ratio 47.33) and CT (from 19 HU to 72 HU) guidances without the occurrences of focal nodules or dysfunction. For the cirrhotic liver and HCC, pronounced enhancement under MR and CT guidance could be seen in liver parenchyma with highlighted lesions after Fe3O4-Au injection. Furthermore, pathological, hematological and biochemical analysis revealed the absence of acute and chronic toxicity, confirming the biocompatibility of our platform for in vivo applications. Collectively, These Fe3O4-Au nanoparticles showed great promise as a candidate for multi-modality bio-imaging.

X-ray CT guided fault-free photothermal ablation of metastatic lymph nodes with ultrafine HER-2 targeting W18O49 nanoparticles.

Designing high accuracy in the diagnosing and fault-freely eliminating lymphatic metastasis of breast malignancy, to avoid the invasiveness and complications caused by traditional assays, is of great therapeutic importance. To this end, theranostic W18O49 nanoparticles targeting to human epidermal growth receptor 2 (HER-2) over-expressed breast malignancy were synthesized via polyol method. By taking advantage of their high X-ray attenuating and photothermotherapy potency, lymph nodes in the mice bearing HER-2 positive metastasis could be clearly distinguished under CT guidance and selectively eliminated by laser ablation. The therapeutic efficacy was further confirmed by the significantly extended survival period. These finding evidenced the potential of these nanoparticles for imaging guided photothermal ablation of HER-2 positive breast malignancy.

X-ray CT and pneumonia inhibition properties of gold-silver nanoparticles for targeting MRSA induced pneumonia.

Non-invasive assay for the early stage diagnosis of methicillin resistant Staphylococcus aureus (MRSA) related pneumonia is of great clinical importance and still a great challenge. In this paper, we reported a novel kind of Au@Ag core-shell theranostic nanoparticles (NPs) conjugated with MRSA specific antibody on their surface. Compared with the raw Au@Ag NPs, these antibody modified NPs (AAMA NPs) showed 10.66 fold enhancement targeting to the MRSA in vitro. In vivo target efficacy was measured with rats bearing pneumonia induced by different pathogens. Computed tomography (CT) results revealed that these AAMA NPs had higher CT contrast enhancement (498 HU), than those of raw Au@Ag and Omnipaque (oth <100 HU). In addition, lesions labeled by AAMA NPs could be distinguished from lung parenchyma by taking advantage of spectra CT. Bio-distribution analysis confirmed that these AAMA NPs accumulated in the MRSA rich site. Both BAL and Elisa assays indicated that these AAMA NPs greatly alleviated the inflammation reaction by reducing bacterial proliferation and cytokine production. Pathological study showed that these NPs exerted negligible long term cytotoxicity in vivo.

Fabrication of Au@Ag core-shell NPs as enhanced CT contrast agents with broad antibacterial properties

Au@Ag core-shell nanoparticles (NPs) integrating both antibacterial and X-ray attenuation capabilities were facilely synthesized in aqueous solution. These NPs modified with methoxy-PEG-SH (m-PEG) on the surface rendered them favorable dispersity and stability in water, resulting in enhancement of their blood circulation time. X-ray photoelectron spectroscope (XPS) and high-resolution transmission electron microscope (HRTEM) results confirmed the core-shell structure of m-PEG-Au@Ag NPs. The m-PEG-Au@Ag NPs showed low cytotoxicity and strong X-ray absorption potency in vitro. Further in vivo study showed that as-synthesized NPs offered a pronounced contrast and prolonged their circulation time in the blood stream with negligible toxic effect in vivo. Besides, m-PEG-Au@Ag NPs had significant bacteriostatic effect toward common bacteria like Escherichia coli and Staphylococcus aureus as demonstrated by broth dilution assay. Given their low-cytotoxicity and high CT attenuation efficacy, m-PEG-Au@Ag NPs had a promising potential for use as CT enhancing and antibacterial agents.

Multifunctional Bi2WO6 Nanoparticles for CT-Guided Photothermal and Oxygen-Free Photodynamic Therapy

The consumption of oxygen in photodynamic therapy (PDT) significantly exacerbates the degree of hypoxia in tumors, which not only impedes the therapeutic effect of PDT, but also drives local tumor recurrence. To relieve the PDT-induced hypoxia and improve the therapeutic outcome of PDT in cancer treatment, herein we reported a class of Bi2WO6 nanoparticles (NPs) as a robust multifunctional platform, which integrates the abilities for contrast-enhanced computed tomography (CT) imaging, photothermal therapy, and PDT in an oxygen-free manner. The as-obtained Bi2WO6 NPs with a mean diameter of 5.2 nm are stable in phosphate-buffered saline and an in vivo microenvironment-mimicking buffer. The location of the solid tumor could be accurately positioned using Bi2WO6-enhanced CT with higher spatial resolution. After being irradiated with an 808 nm laser, these Bi2WO6 NPs could realize CT-guided local photothermal ablation of the tumor. Meanwhile, •OH radicals were generated simultaneously from the treatment without consuming an oxygen molecule, which enabled these Bi2WO6 NPs to exert photodynamic killing effect in an oxygen-free manner during cancer therapy. Remarkable tumor suppression was observed in mice bearing the HeLa xenograft, supporting the promising application of these multifunctional Bi2WO6 NPs in the combat against cancers through synergistic photothermal and oxygen-free PDT treatment.

Hypoxia-Targeting, Tumor Microenvironment Responsive Nanocluster Bomb for Radical-Enhanced Radiotherapy

Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment-targeting NPs (∼5 nm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced computed tomography (CT) with higher spatial resolution. Once irradiated with a 1064 nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia-induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment in hypoxic tumor management.

Silver nanoshells as tri-mode bactericidal agents integrating long term antibacterial, photohyperthermia and triggered Ag+ release capabilities

Novel polymer–silver hybrid core–shell nanoparticles (SNSs) which showed long term bacteriostatic, photohyperthermia induced bactericidal and triggered Ag+ release abilities were reported. Both gram-negative (GN) and gram-positive (GP) bacteria can be effectively killed by photothermolysis therapy. The Ag+ release triggered by illumination provides a sustained release of Ag+, which offers long term antibacterial ability under normal conditions.

Doxorubicin loaded chitosan–ZnO hybrid nanospheres combining cell imaging and cancer therapy

We report chitosan–ZnO nanoparticles (CZNPs), which have enhanced photoluminescence stability and longer retention time in cells compared with pure ZnO QDs. These CZNPs can illuminate the cells, show the distribution of the nanospheres in the cell, and thus monitor the fate of the loaded drug, which enable these CZNPs to have a promising future in cell imaging and cancer therapy.

Ultra-sensitive diagnosis of orthotopic patient derived hepatocellular carcinoma by Fe@graphene nanoparticles in MRI

We synthesized core–shell structured Fe/G-PEG NPs composed of an Fe core and a PEGylated graphene, which exhibited superior stability against oxidation, good water dispersity, low cytotoxicity and high magnetic performance. These advantages ensure them as candidates for ultra-sensitive contrast enhanced magnetic resonance imaging agents in vivo.