Zhenghuan Zhao

OCTAPOD IRON OXIDE NANOPARTICLES AS HIGH PERFORMANCE T2 CONTRAST AGENTS FOR MAGNETIC RESONANCE IMAGING

Spherical superparamagnetic iron oxide nanoparticles have been developed as T2-negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3 ± 30 mM(-1) s(-1)), indicating that these octapod iron oxide nanoparticles are much more effective T2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic.

Nanoprobes for in vitro diagnostics of cancer and infectious diseases.

The successful and explosive development of nanotechnology is significantly impacting the fields of biology and medicine. Among the spectacular developments of nanobiotechnology, interest has grown in the use of nanomaterials as nanoprobes for bioanalysis and diagnosis. Herein, we review state-of-the-art nanomaterial-based probes and discuss their applications in in vitro diagnostics (IVD) and challenges in bringing these fields together. Major classes of nanoprobes include quantum dots (QDs), plasmonic nanoparticles, magnetic nanoparticles, nanotubes, nanowires, and multifunctional nanomaterials. With the advantages of high volume/surface ratio, surface tailorability, multifunctionality, and intrinsic properties, nanoprobes have tremendous applications in the areas of biomarker discovery, diagnostics of infectious diseases, and cancer detection. The distinguishing features of nanoprobes for in vitro use, such as harmlessness, ultrasensitivity, multiplicity, and point-of-care use, will bring a bright future of nanodiagnosis.

Magnetite nanoparticles as smart carriers to manipulate the cytotoxicity of anticancer drugs: magnetic control and pH-responsive release

We described the smart and targeted magnetic nanocarriers to control the delivery and release of anticancer drug doxorubicin (DOX) in vitro and demonstrated that they can exhibit much higher cytotoxicity to cancer cells than free DOX. The conjugation of targeted magnetite nanoparticles (∼14 nm in diameter) and DOX molecule via acid-labile imine bond endows the nanocarriers with three advanced features: magnetically controllable, specific targeting, and pH-responsive. The cell toxicity assays indicated the pH-sensitive magnetic nanocarriers (IC50 of 0.13 μg mL−1 to HeLa cells) have much higher anticancer activity than free DOX (IC50 of 1.16 μg mL−1 to HeLa cells). Moreover, the magnetically guided delivery of nanocarriers can further improve the drug efficacy (IC50 of ∼0.087 μg mL−1 to HeLa cells). The arginine–glycine–aspartic acid (RGD)-modified magnetic nanocarriers recognized the specific cells effectively (IC50 of 0.93 μg mL−1 to U-87 MG cells) and showed the increased cytotoxicity to cancer cells under external magnetic fields. This intelligent (magnetically guided, molecular targeted, and pH-responsive) drug delivery system has the ability to improve the chemotherapeutic efficacy and reduce the side effects, which has a great potential to become a favorable strategy for delivery of drugs to the desired sites in patients.

Surface and Interfacial Engineering of Iron Oxide Nanoplates for Highly Efficient Magnetic Resonance Angiography

Magnetic resonance angiography using gadolinium-based molecular contrast agents suffers from short diagnostic window, relatively low resolution and risk of toxicity. Taking into account the chemical exchange between metal centers and surrounding protons, magnetic nanoparticles with suitable surface and interfacial features may serve as alternative T1 contrast agents. Herein, we report the engineering on surface structure of iron oxide nanoplates to boost T1 contrast ability through synergistic effects between exposed metal-rich Fe3O4(100) facets and embedded Gd2O3 clusters. The nanoplates show prominent T1 contrast in a wide range of magnetic fields with an ultrahigh r1 value up to 61.5 mM(-1) s(-1). Moreover, engineering on nanobio interface through zwitterionic molecules adjusts the in vivo behaviors of nanoplates for highly efficient magnetic resonance angiography with steady-state acquisition window, superhigh resolution in vascular details, and low toxicity. This study provides a powerful tool for sophisticated design of MRI contrast agents for diverse use in bioimaging applications.

Multifunctional Ag@Fe2O3 yolk–shell nanoparticles for simultaneous capture, kill, and removal of pathogen

We combined silver and iron oxide nanoparticles to make unique Ag@Fe2O3 yolk–shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe2O3–Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe2O3 yolk–shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.

Real-Time Monitoring of Arsenic Trioxide Release and Delivery by Activatable T1 Imaging

Delivery of arsenic trioxide (ATO), a clinical anticancer drug, has drawn much attention to improve its pharmacokinetics and bioavailability for efficient cancer therapy. Real-time and in situ monitoring of ATO behaviors in vivo is highly desirable for efficient tumor treatment. Herein, we report an ATO-based multifunctional drug delivery system that efficiently delivers ATO to treat tumors and allows real-time monitoring of ATO release by activatable T1 imaging. We loaded water-insoluble manganese arsenite complexes, the ATO prodrug, into hollow silica nanoparticles to form a pH-sensitive multifunctional drug delivery system. Acidic stimuli triggered the simultaneous release of manganese ions and ATO, which dramatically increased the T1 signal (bright signal) and enabled real-time visualization and monitoring of ATO release and delivery. Moreover, this smart multifunctional drug delivery system significantly improved ATO efficacy and strongly inhibited the growth of solid tumors without adverse side effects. This strategy has great potential for real-time monitoring of theranostic drug delivery in cancer diagnosis and therapy.

Understanding the metabolic fate and assessing the biosafety of MnO nanoparticles by metabonomic analysis

Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, (1)H NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development.

Kinetic and sensitive analysis of tyrosinase activity using electron transfer complexes: in vitro and intracellular study

Tyrosinase is an important marker of human diseases such as the neurodegeneration associated with Parkinsons disease and melanoma. Sensitive detection of tyrosinase activity in vitro and inside cells is of great significance to medical diagnostics and skin disorder treatments. With unique photophysical properties, semiconductor quantum dots (QDs) are employed as photoluminescent platforms for various biosensing, in particular for the detection of enzyme activities. In this work, QDs are functionalized with tyrosine and zwitterionic molecules to construct a nanometer-scale scaffold (QD-Tyr conjugate), and this is used to test tyrosinase activity in vitro and inside cells. Tyrosinase oxidizes tyrosine to dopachrome and switches on the electron-transfer access, which relates to fluorescence quenching. High quenching efficiency is achieved by shortening the distance between the electron donors and acceptors, which is attributed to the small size of the conjugated tyrosine. Enzymatic process curves reveal the enhanced enzymatic activity on the conjugated nanoparticle substrate, which leads to highly sensitive detection of tyrosinase (as low as 1 nM). It is also demonstrated that QD-Tyr conjugates can sensitively probe intracellular tyrosinase in melanoma cells, which promises great potential in disease monitoring and medical diagnostics.

Theranostic Au Cubic Nano-aggregates as Potential Photoacoustic Contrast and Photothermal Therapeutic Agents

Multifunctional nanostructures combining diagnosis and therapy modalities into one entity have drawn much attention in the biomedical applications. Herein, we report a simple and cost-effective method to synthesize a novel cubic Au nano-aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong near-infrared (NIR) absorption, excellent water-solubility, good photothermal stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min, the temperature of the solution containing Au-80 CNAs (100 μg/mL) increased by ~38 °C. The in vitro and in vivo studies demonstrated that Au-80 CNAs could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs shows great potentials for theranostic applications. Moreover, this facile and cost-effective synthetic method provides a new strategy to prepare stable Au nanomaterials with excellent optical properties for biomedical applications.

Facile, sensitive, and ratiometric detection of mercuric ions using GSH-capped semiconductor quantum dots

Glutathione (GSH) capped CdTe semiconductor quantum dots (QDs) are applied for detecting mercuric ions (Hg(2+)) of trace quantity. The synthesis of GSH-capped CdTe (CdTe@GSH) QDs is cost-efficient and straightforward. We observed that Hg(2+) can quantitatively quench the fluorescence of CdTe@GSH QDs and further induce the slight redshift of emission peaks due to the quantum confinement effect. Detailed studies by spectroscopy, dynamic light scattering (DLS), and electrospray ionization mass spectrometry (ESI-MS) demonstrated that the competitive Hg(2+) binding with GSH makes the surface of CdTe QDs exposed, results in gradual aggregation, and quantitatively changes the photophysical properties of QDs. The whole procedure for detecting Hg(2+) by this protocol took less than 10 min. The experimental limit of detection (LOD) of Hg(2+) can be as low as 5 nM using CdTe@GSH with a low concentration (0.5 nM) because of the excellent fluorescent properties of QDs. This strategy may become a promising means to simply detect Hg(2+) in water with high sensitivity.