Xiangpeng Zheng

Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging

Early diagnosis probes that combine fluorescence, X-ray computed tomography (CT) and magnetic resonance (MR) imagings are anticipated to give three dimensional (3D) details of tissues and cells of high resolution and sensitivity. However, how to combine these three modalities together within a sub-50 nm sized structure is technically challenging. Here we report a trimodal imaging probe of PEGylated NaY/GdF(4): Yb, Er, Tm @SiO(2)-Au@PEG(5000) nanopaticles of uniform size of less than 50 nm. The as-designed nanoprobes showed (1) strong emissions ranging from the visible (Vis) to near infrared (NIR) for fluorescent imaging, (2) T(1)-weighted MRI by shorting T(1) relaxation time and (3) enhanced HU value as a CT contrast agent. The structure was optimized based on a comprehensive investigation on the influence of the distance between the NaY/GdF(4): Yb, Er, Tm core and Au nanoparticles (NPs) at the surface. The potential of trimodal imaging for cancerous cells and lesions was further demonstrated both in vitro and in vivo.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Intelligent MnO2 Nanosheets Anchored with Upconversion Nanoprobes for Concurrent pH-/H2O2-Responsive UCL Imaging and Oxygen-Elevated Synergetic Therapy.

Dr. W. Fan, Prof. W. Bu, Dr. Q. He, Dr. Z. Cui, Dr. Y. Liu, Prof. J. Shi State Key Laboratory of High Performance Ceramics and Superfi ne Microstructures Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 , P. R. China E-mail: wbbu@mail.sic.ac.cn; jlshi@mail.sic.ac.cn Prof. W. Bu Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites Nanjing Tech University Nanjing 210009 , P. R. China Dr. B. Shen Institute of Radiation Medicine Fudan University Shanghai 200032 , P. R. China Dr. X. Zheng Department of Radiation Oncology Shanghai Huadong Hospital Fudan University Shanghai 200040 , P. R. China Dr. K. Zhao Department of Radiology Shanghai Cancer Hospital Fudan University Shanghai 200032 , P. R. China

A NaYbF4: Tm3+ nanoprobe for CT and NIR-to-NIR fluorescent bimodal imaging

Early diagnosis that combines the high-resolutional CT and sensitive NIR-fluorescence bioimaging could provide more accurate information for cancerous tissues, which, however, remain a big challenge. Here we report a simple bimodal imaging platform based on PEGylated NaYbF(4): Tm(3+) nanoparticles (NPs) of less than 20 nm in diameter for both CT and NIR-fluorescence bioimaging. The as-designed nanoprobes showed excellent in vitro and in vivo performances in the dual-bioimaging, very low cytotoxicity and no detectable tissue damage in one month. Remarkably, the Yb(3+) in the lattice of NaYbF(4): Tm(3+) NPs functions not only as a promising CT contrast medium due to its high X-ray absorption coefficiency, but also an excellent sensitizer contributing to the strong NIR-fluorescent emissions for its large NIR absorption cross-section. In addition, these NPs could be easily excreted mainly via feces without detectable remnant in the animal bodies.

Radiopaque fluorescence-transparent TaOx decorated upconversion nanophosphors for in vivo CT/MR/UCL trimodal imaging

To address the intractable issues such as the low performance or biocompatibility frequently encountered in previous CT, magnetic resonance (MR) and fluorescence trimodal imaging nanoprobes, a nanocomposite has been constructed by decorating gadolinium ions doped upconversion nanoparticle (Gd-doped UCNP) with radiopaque but fluorescence-transparent tantalum oxide (TaO(x), x ≈ 1). The as-synthesized water-soluble nanoparticle showed a litchi-like shape with an average size of ~30 nm and demonstrated extraordinarily high longitudinal and transverse relaxivity values (r(1) = 11.45 mM(-1)s(-1) and r(2) = 147.3 mM(-1)s(-1)) compared with the reported Gd-doped UCNPs to date. Obvious CT contrast enhancement was obtained by the combined effect between the radiopaque TaO(x) shell and the Gd-doped UCNP inner core. Strong upconversion luminescence (UCL) signal could unobstructedly penetrate out in virtue of high transparency of the TaO(x) shell. No mutual interference among different modalities of the upconversion nanolitchi (UCNL) was found, which ensured that the individual merits of every imaging modality could be brought into full play, demonstrated by in vitro and in vivo imagings. Furthermore, UCNLs showed only a slight effect on macrophages and RBCs in vitro and tissue in vivo.

Ultrasmall NaGdF4 Nanodots for Efficient MR Angiography and Atherosclerotic Plaque Imaging

Dr. H. Xing, Prof. W. Bu, Dr. L. Wang, Dr. Q. Xiao, Dr. D. Ni, Prof. J. Shi State Key Laboratory of High Performance Ceramics and Superfi ne Microstructure Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 , P.R. China E-mail: wbbu@mail.sic.ac.cn; jlshi@mail.sic.ac.cn Dr. S. Zhang, Prof. L. Zhou, Prof. W. Peng, Prof. K. Zhao Department of radiology Shanghai Cancer Hospital Fudan University Shanghai 200032 , P.R. China Prof. X. Zheng, Prof. Y. Hua Department of radiation oncology Shanghai Huadong Hospital Fudan University Shanghai 200040 , P.R. China Dr. J. Zhang Shanghai (Red Cross) Blood Center Shanghai Institute of Blood Transfusion Shanghai 200051 , P.R. China

A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery

The early diagnosis and simultaneous drug delivery monitored by non-invasive visualization are highly challenging but clinical-relevant for the diagnostics and therapy monitoring of serious diseases such as cancers. Herein, a Gd-doped layered double hydroxide (LDH)/Au nanocomposite has been developed as both a drug carrier and a diagnostic agent. The obtained nanocomposite shows high non-anionic anti-cancer drug DOX loading capacity and an interesting pH-responsive release profile of loaded DOX. The nanocomposite was found to be able to efficiently transport DOX into the cancer cell, release the DOX in the acidic cytoplasm and then cause death of cancer cells. Meanwhile, the nanocomposite demonstrates better in vitro CT and T(1)-weighted MR imaging capabilities than the commercial MRI and CT contrast agents and favorable in vivo CT and T(1)-weighted MR imaging performance. After being modified with heparin, the nanocomposite also demonstrates effective CT and MR imagings of tumors by intravenous administration in tumor-bearing mice. Furthermore, the nanocomposite shows negligible cytotoxicity and no detectable tissue damage on mice after injection of high dosage of nanocomposite. In conclusion, the synthetic nanocomposite is expected to be a potential theranostic agent for bimodal imagings of cancers and anti-cancer drug delivery as well.

Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements

The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er3+ nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues.

Dual-energy Computed Tomography Imaging of Thyroid Nodule Specimens: Comparison With Pathologic Findings

Objective:To quantitatively assess the imaging characteristics of thyroid nodules in dual-energy computed tomography (CT) imaging for differentiation of benign and malignant lesions. Materials and Methods:Dual-energy CT imaging was performed on 97 surgically removed thyroid nodule specimens prior to their pathologic examination. Iodine- and water-based material decomposition images and 101 sets of pseudomonochromatic images of each thyroid specimen were reconstructed for quantitative imaging analysis. The iodine concentration and effective atomic number (Zeff) of thyroid nodules and surrounding normal thyroid tissues, HU curve slope (&lgr;HU), and mean CT values of nodules were compared between different pathologic categories. Results:In the 97 specimens, a total of 169 nodules were confirmed pathologically, including 108 nodular goiters (group A), 47 follicular adenomas (group B), and 14 papillary carcinomas (group C). Statistical analysis showed a significant difference between benign (A and B) and malignant (C) groups in iodine concentration (P < 0.001), &lgr;HU (P < 0.001), and Zeff (P < 0.001). For mean CT values, there existed statistical difference between groups A and C, but no difference between groups B and C. No statistical significance was found at iodine concentrations, the Zeff, or &lgr;HU in thyroid tissues surrounding nodules (P > 0.10). Additionally, water content was constant and homogeneous in nodules and adjacent thyroid tissues (P > 0.10). Conclusion:Pseudomonochromatic imaging reconstruction and material decomposition-based quantitative dual-energy CT imaging have promising potential for diagnostic differentiation of benign and malignant thyroid nodules.

Single W18O49 nanowires: A multifunctional nanoplatform for computed tomography imaging and photothermal/photodynamic/radiation synergistic cancer therapy

Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensitizers, or dose intensifiers for photothermal therapy (PTT), photodynamic therapy (PDT), or radiation therapy (RT). In this study, ultrathin tungsten oxide nanowires (W18O49) were synthesized using a solvothermal approach and examined as a multifunctional theranostic nanoplatform. In vitro and in vivo analyses demonstrated that these nanowires could induce extensive heat- and singlet oxygen-mediated damage to cancer cells under 980 nm near infrared (NIR)-laser excitation. They were also shown to function as radiation dose intensifying agents that enhance irradiative energy deposition locally and selectively during radiation therapy. Compared to NIR-induced PTT/PDT and RT alone, W18O49-based synergistic tri-modal therapy eradicated xenograft tumors and no recurrence was observed within a 9-month follow up. Moreover, the strong X-ray attenuation ability of the tungsten element (Z = 74, 4.438 cm2·g–1, 100 KeV) qualified these nanowires as excellent contrast agents in X-ray-based imaging, such as diagnostic computed tomography (CT) and cone-beam CT for image-guided radiation therapy. Toxicity studies demonstrated minimal adverse effects on the hematologic system and major organs of mice within one month. In conclusion, these nanowires have shown significant potential for cancer therapy with inherent image guidance and synergistic effects from phototherapy and radiation therapy, which warrants further investigation.