Jianfeng Zeng

Magnetic/Upconversion Fluorescent NaGdF4:Yb,Er Nanoparticle-Based Dual-Modal Molecular Probes for Imaging Tiny Tumors in Vivo

Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a click reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.

Anchoring Group Effects of Surface Ligands on Magnetic Properties of Fe3O4 Nanoparticles: Towards High Performance MRI Contrast Agents

The effect of the anchoring group of surface ligands on the magnetic properties, especially relaxometric properties, of PEGylated Fe₃ O₄ nanoparticles is investigated. Systematic experimental results together with in-depth theoretical analysis reveal that the ligand binding affinity can largely vary the saturation magnetization, whereas conjugated anchoring groups can remarkably enhance the transverse relaxivity, which highlights a novel approach for achieving high-performance MRI contrast agents.

Gelification: An Effective Measure for Achieving Differently Sized Biocompatible Fe3O4 Nanocrystals through a Single Preparation Recipe

Biocompatible Fe(3)O(4) nanocrystals were synthesized through the pyrolysis of ferric acetylacetonate (Fe(acac)(3)) in diphenyl oxide, in the presence of α,ω-dicarboxyl-terminated polyethylene glycol (HOOC-PEG-COOH) and oleylamine. Unusual gelification phenomena were observed from the aliquots extracted at different reaction stages after they were cooled to room temperature. By reaction time, the average size of the Fe(3)O(4) nanocrystals was tuned from 5.8 to 11.7 nm with an equilibrium size around 11.3 nm. By increasing the gelification degree of the stock solution, the equilibrium size of the Fe(3)O(4) nanocrystals was further increased from 11.3 to 18.9 nm. The underlying gel formation mechanism was investigated by using ultraviolet-visible absorption spectroscopy and Fourier transform infrared spectroscopy. The results suggest that the complexation between HOOC-PEG-COOH and Fe(acac)(3), with the help of oleylamine, results in large molecular networks, which are responsible for the gelification of the stock solution, while the interaction between the fragment of the molecular network and Fe(3)O(4) nanocrystal is responsible for the second gelification process observed during the early stage of reflux. To further investigate the particle growth behavior, small molecules released during the preparation were collected and analyzed by using photoelectron spectroscopy/photoionization mass spectroscopy (PES/PIMS). It was demonstrated that the pyrolysis of the Fe precursor is strongly correlated with the particle growth process. Further numerical simulations reveal that the first gelification process induced by the complexation between HOOC-PEG-COOH and Fe(acac)(3) largely alters the pyrolysis behavior of the Fe precursor; consequently, the equilibrium size of the resultant Fe(3)O(4) nanocrystals can effectively be tuned by the gelification degree of the stock solution.

Ultrasmall Biocompatible Bi2Se3 Nanodots for Multimodal Imaging-Guided Synergistic Radiophotothermal Therapy against Cancer.

Sub-3 nm ultrasmall Bi2Se3 nanodots stabilized with bovine serum albumin were successfully synthesized through a reaction of hydroxyethylthioselenide with bismuth chloride in aqueous solution under ambient conditions. These nanodots exhibit a high photothermal conversion efficiency (η = 50.7%) due to their strong broad absorbance in the near-infrared (NIR) window and serve as a nanotheranostic agent for photoacoustic imaging and photothermal cancer therapy. In addition, they also display radioenhancement with a ratio of 6% due to their sensitivity to X-rays, which makes them a potential sensitizer for radiotherapy. These nanodots were also labled with radioactive 99mTc for quantification of their biodistribution by single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging. Our work demonstrates the potential of ultrasmall Bi2Se3 nanodots in multimodal imaging-guided synergetic radiophotothermal therapy of cancer.

Insight into Strain Effects on Band Alignment Shifts, Carrier Localization and Recombination Kinetics in CdTe/CdS Core/Shell Quantum Dots

The impact of strain on the optical properties of semiconductor quantum dots (QDs) is fundamentally important while still awaiting detailed investigation. CdTe/CdS core/shell QDs represent a typical strained system due to the substantial lattice mismatch between CdTe and CdS. To probe the strain-related effects, aqueous CdTe/CdS QDs were synthesized by coating different sized CdTe QD cores with CdS shells upon the thermal decomposition of glutathione as a sulfur source under reflux. The shell growth was carefully monitored by both steady-state absorption and fluorescence spectroscopy and transient fluorescence spectroscopy. In combination with structural analysis, the band alignments as a consequence of the strain were modified based on band deformation potential theory. By further taking account of these strain-induced band shifts, the effective mass approximation (EMA) model was modified to simulate the electronic structure, carrier spatial localization, and electron-hole wave function overlap for comparing with experimentally derived results. In particular, the electron/hole eigen energies were predicted for a range of structures with different CdTe core sizes and different CdS shell thicknesses. The overlap of electron and hole wave functions was further simulated to reveal the impact of strain on the electron-hole recombination kinetics as the electron wave function progressively shifts into the CdS shell region while the hole wave function remains heavily localized in CdTe core upon the shell growth. The excellent agreement between the strain-modified EMA model with the experimental data suggests that strain exhibits remarkable effects on the optical properties of mismatched core/shell QDs by altering the electronic structure of the system.

Ultrasmall Magnetic CuFeSe2 Ternary Nanocrystals for Multimodal Imaging Guided Photothermal Therapy of Cancer

Nanoscale ternary chalcogenides have attracted intense research interest due to their wealth of tunable properties and diverse applications in energy and environmental and biomedical fields. In this article, ultrasmall magnetic CuFeSe2 ternary nanocrystals (<5.0 nm) were fabricated in the presence of thiol-functionalized poly(methacrylic acid) by an environmentally friendly aqueous method under ambient conditions. The small band gap and the existence of intermediate bands lead to a broad NIR absorbance in the range of 500-1100 nm and high photothermal conversion efficiency (82%) of CuFeSe2 nanocrystals. The resultant CuFeSe2 nanocrystals show superparamagnetism and effective attenuation for X-rays. In addition, they also exhibit excellent water solubility, colloidal stability, biocompatibility, and multifunctional groups. These properties enable them to be an ideal nanotheranostic agent for multimodal imaging [e.g., photoacoustic imaging (PAI), magnetic resonance imaging (MRI), computed tomography (CT) imaging] guided photothermal therapy of cancer.

Dual-Ratiometric Target-Triggered Fluorescent Probe for Simultaneous Quantitative Visualization of Tumor Microenvironment Protease Activity and pH in Vivo

The abnormal expression of tumor-associated proteases and lowered extracellular pH are important signatures strongly associated with cancer invasion, progression, and metastasis. However, their malignant effects were mainly identified using cell and tissue studies. To noninvasively visualize the heterogeneous distribution of these abnormal indicators in vivo and further disclose their collective behaviors, a target-triggered fluorescent nanoprobe composed of a ratiometric pH-sensitive dye, a near-infrared dye (Cy5.5), and biocompatible Fe3O4 nanoparticles was constructed. The pH-sensitive dye was linked through a peptide substrate of matrix metalloprotease-9 (MMP-9) with Fe3O4 nanoparticles to establish a Förster resonance energy transfer (FRET) system for sensing the pH of the tumor microenvironment. Cy5.5 served as an internal reference for forming a secondary ratiometric fluorescent system together with the activated pH dye to enable the visualization of protease activities in vivo. Extensive imaging studies using a mouse model of human colon cancer revealed that the overexpression of MMP-9 and abnormal microenvironmental pH quantitatively visualized by this dual-ratiometric probe are spatially heterogeneous and synergistically guide the tumor invasion in vivo.