Dengtong Huang

A synergistically enhanced T1-T2 dual-modal contrast agent

Monodisperse Gd(2) O(3) -embedded iron oxide (GdIO) nanoparticles can simultaneously enhance the local magnetic field intensities of each other under an external magnetic field and result in synergistic enhancement of T(1) and T(2) effects. GdIO nanoparticles have the unique property to be both T(1) and T(2) contrast agents and can potentially lead to higher accuracy in cancer diagnosis, particularly liver tumors.

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.

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.

Nanoparticles modulate autophagic effect in a dispersity-dependent manner.

Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy, and offer a new alternative way to modulate autophagy.

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.

A Synergistically Enhanced T-1-T-2 Dual-Modal Contrast Agent

Monodisperse Gd(2) O(3) -embedded iron oxide (GdIO) nanoparticles can simultaneously enhance the local magnetic field intensities of each other under an external magnetic field and result in synergistic enhancement of T(1) and T(2) effects. GdIO nanoparticles have the unique property to be both T(1) and T(2) contrast agents and can potentially lead to higher accuracy in cancer diagnosis, particularly liver tumors.

Silica nanovehicles endow arsenic trioxide with an ability to effectively treat cancer cells and solid tumors

Arsenic trioxide is a clinical drug that can be used to successfully treat acute promyelocytic leukemia. However, its therapeutic effect on solid tumors is limited because of the poor pharmacokinetics and dose-limiting toxicity. Here, we report a facile strategy to achieve high anticancer activity of arsenic trioxide by loading the nanoparticulate prodrug into hollow silica inorganic nanoparticles. Because of the appropriate size, pH sensitivity, and surface targeted modification, this smart nanosized drug system can deliver arsenic trioxide into cancer cells efficiently and exhibits much higher cytotoxicity to a variety of cancer cells than free arsenic trioxide. Moreover, this nanomedicine can further promote the differentiation and inhibit the migration of cancer cells. In vivo results suggest that this drug delivery system can significantly inhibit the growth of solid tumors without adverse side effects. This study highlights a feasible drug delivery strategy to expand the use of arsenic trioxide for the effective treatment of solid tumors.

Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells.

Silica sub-microspheres induce autophagy in an endocytosis dependent manner

The health risk of exposure to manufactured nano- and submicro-materials leads to an increasing effort to explore their biological effects and potential toxicity in detail. Here, we show that silica sub-microspheres (0.1 to 2.1 μm in diameter), the major component of dust or particulate matter less than 2.5 μm (PM 2.5), induce autophagy depending on the levels of cellular endocytosis. Due to the suitable size for cellular endocytosis, 0.5–0.7 μm silica particles induce the highest levels of autophagy among particles from 0.1 to 2.1 μm in diameter. Changes in cellular endocytosis of silica sub-microspheres lead to alteration of autophagy levels. Furthermore, dephosphorylation of FOXO3A and subsequent translocation to the nucleus may be associated with this autophagy process. Our results reveal the manner in which silica sub-microspheres induce autophagy, emphasize the potential risk of endocytosis of fine particles or other non-degradable materials, and suggest a new signaling pathway involved with autophagy induced by sub-micromaterials.