Shengping Gao

Near-infrared fluorescence imaging of cancer cells and tumors through specific biosynthesis of silver nanoclusters

Human life toll by cancer, one of the highest among most dreaded diseases in advanced societies, could be reduced by implementing evidence-based strategies for its prevention, early diagnosis and assessment of the progress and suitability of therapies by fast and non-invasive methods. In this contribution, a novel strategy is reported for highly sensitive recognition and in vivo imaging of cancer cells taking advantage of their spontaneous ability to generate silver nanoclusters (NCs) with high near-infrared fluorescence emission by intracellular reduction of innocuous silver salts. Both ex vivo experiments comparing cancer cell models to normal cells and in vivo imaging of subcutaneous xenografted tumor (cervical carcinoma model) in nude mice established the validity of this strategy for precise and selective imaging of cells and tumors. Furthermore, it was observed that the spontaneous self-generation of Ag NCs by tumors in their inside led to drastic reduction of their sizes and often to complete remission, thus providing important hope for new therapy strategies based on cheap and readily available agents.

Antimicrobial activity of a ferrocene-substituted carborane derivative targeting multidrug-resistant infection.

Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to threaten the health of human beings. Developing new antibacterial agents, therefore, are urgently needed. Herein, we have explored the possibility to design and synthesize some novel antibacterial agents including ferrocene-substituted carborane derivative (Fc(2)SBCp(1)) and have evaluated the relevant antibacterial action against two clinical common MDR pathogens (i.e., Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro and in vivo. The results demonstrate that in vitro antimicrobial activity of Fc(2)SBCp(1) could be gradually transformed into a bactericidal effect from a bacteriostatic effect with the increasing concentration of the active carborane derivative, which can also prevent biofilm formation at concentrations below MIC (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that there exists no/or little toxic effect of Fc(2)SBCp(1) on normal cells/tissues and leads to little hemolysis. In vivo studies illustrate that the new carborane derivative Fc(2)SBCp(1) is highly effective in treating bacteremia caused by S. aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus. This raises the possibility for the potential utilization of the new ferrocene-substituted carborane derivatives as promising antibacterial therapeutic agents against MDR bacterial infections in future clinical applications.

Simultaneous and multisite tumor rapid-target bioimaging through in vivo biosynthesis of fluorescent gold nanoclusters

Simultaneous and multisite tumor rapid-target bioimaging has been realized in this contribution through in vivo biosynthesis of fluorescent gold nanoclusters (GNCs). The selectively biosynthesized fluorescent GNCs in cancer cells or tumor tissues by systemic bio-administration of gold precursors via tail vein injection in tumor bearing mice were found to exhibit a highly efficient tumor targeting effect. Intracellular fluorescence studies demonstrate that in vivo biosynthesized GNCs from cancer cells could efficiently label and image target cells with bright photostable fluorescence, which could be readily exploited for the rapid imaging in vivo of the biodistribution of GNCs in mice and thus efficiently determine the precise target sites of fluorescent GNCs specifically biosynthesized in tumor tissues with high spatiotemporal resolution. Moreover, histopathologic analyses of H&E-stained tissue sections indicate that no side effects for mice treated with gold precursors are found during the process of systemic bio-administration for gold precursors. This raises the possibility of utilizing the in vivo biosynthesized GNCs through intravenous administration of biocompatible gold precursors as promising and effective biomarkers for rapid tumor diagnosis and precise surgical intervention.

One-step rapid synthesis of fluorescent platinum nanoclusters for cellular imaging and photothermal treatment

Fluorescent platinum nanoclusters constructed through one-step synthesis from chloroplatinic acid cross swiftly across carcinoma cell membranes for bio-imaging and photothermal treatment.

New strategy for reversing biofilm-associated antibiotic resistance through ferrocene-substituted carborane ruthenium(II)-arene complex

Bacterial biofilms are inherently resistant to antimicrobial agents and are difficult to eradicate with conventional antimicrobial agents, resulting in many persistent and chronic bacterial infections. In this contribution, a new strategy for reversing the biofilm-associated antibiotic resistance has been explored by induction of a carborane ruthenium(II)-arene complex (FcRuSB). Our results demonstrate that the FcRuSB could be utilized as an inducer to efficiently reverse the biofilm-associated antibiotic resistance of multidrug-resistant (MDR) clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa. The induced effect of FcRuSB is correlated with a considerable decrease in the expression of extracellular matrix proteins (EMP) of the two strains. The considerable decrease of the EMP of induced cells, resulting in the reduction of adherence and biofilm formation ability of the two types of MDR pathogens, and then can cause significantly enhanced sensitivity of them to antibiotics.

Novel conjugated Ag@PNIPAM nanocomposites for an effective antibacterial wound dressing

It is well known that nanosilver or silver ions could act as an effective antibacterial agent without the development of bacterial resistance but long term exposure may induce in vivo toxicity. Thus, specific care should be taken before relevant silver-containing materials are used as antibacterial agents. Recently biocompatible polymeric materials are widely used to reduce the toxic effects of nanomaterials, which could be utilized to fabricate antibacterial surface coatings with good biocompatibility. In this study we have developed a simple and green synthesis strategy to prepare Ag@PNIPAM nanocomposites with high purity and good bioactivity for promising bio-applications as highly effective antimicrobial agents. The relevant synthesis takes place in a clean environment without any chemical additives, which ensures ultrahigh active surfaces of the Ag clusters. The as-prepared Ag@PNIPAM nanocomposites exhibit highly effective antimicrobial activities against Staphylococcus aureus (S. aureus) and have a good therapeutic effect for burn wounds.

In-situ green synthesis of highly active GSH-capped Pt-Au-Ag-hybrid nanoclusters

Recently much attention has been paid to the application of metal hybrid nanoparticles in industrial catalytic fields because of their super-efficient catalytic activity and attractive properties. We explored a novel strategy to prepare GSH-capped Pt-Au-Ag-hybrid nanoclusters through the synergistic effect between ascorbic acid (VC) and glutathione (GSH) with chloroplatinic acid, chloroauric acid, and silver nitrate as precursors. The potential utilization of as-prepared GSH-capped Pt-Au-Ag-hybrid nanoclusters for catalytic applications has been evaluated through the reduction of 4-nitrophenol (4-NP) with NaBH4; we obtained the kinetic data by monitoring with UV-Vis spectroscopy. Our results illustrate that GSH-capped Pt-Au-Ag-hybrid nanoclusters could facilitate the process of reduction of 4-NP in a way that is unprecedented. This approach may offer a novel, non-cytotoxicity, efficient catalyst for industry.

Size-controlled porous superparamagnetic Zn1/3Fe8/3O4 nanospheres: synthesis, properties and application for drug delivery

Magnetic nanospheres have recently attracted much attention in the biomedical areas due to their good biocompatibility and unique magnetic features. Herein we report the synthesis and characterization of different sized porous superparamagnetic iron oxide nanospheres (SPIONs) (Zn1/3Fe8/3O4) which are based on a new rational method of elevated-temperature hydrolysis of chelate iron alkoxide complexes in solutions of the corresponding alcohol, diethyleneglycol (DEG) and diethanolamine (DEA). The size of the SPIONs is controlled by changing the ratio of the reaction media. It is noted that the highly water dispersible porous SPIONs with narrow size distribution can be tuned from 6.5 to 200 nm, each of which is composed of many single magnetite crystallites of approximately 5.5 nm in size. The SPIONs show superparamagnetic properties at room temperature. The superparamagnetic behavior, high magnetization, and high water dispersibility make these nanospheres ideal candidates for various important applications for drug delivery.

Novel multifunctional nanospheres of Zn1/3Fe8/3O4@Ag: synthesis, properties and application for multi-modality tumor imaging

New multifunctional nanospheres have been designed and synthesized through a green and facile strategy, which could be readily used in multi-modality tumor imaging through near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) imaging. Such nanospheres are made of porous superparamagnetic Zn1/3Fe8/3O4 nanosphere cores covered by a thin layer shell of Ag clusters. While the shell of Ag clusters provides efficient NIRF imaging, the Zn1/3Fe8/3O4 nanosphere cores allow external magnetic manipulation and readily facilitates their utilization for MRI and CT imaging.