Shih-Chun Wei

Gold nanoparticles (Au NPs) are conjugated with the vascular endothelial growth factor-A₁₆₅ (VEGF-A₁₆₅) and (11-mercaptoundecyl)-N,N,N-trimethylammonium (11-MTA) cation to form dual-functional gold nanoparticles (11-MTA/VEGF-Au NPs) that possess antimicrobial and proangiogenic activities for wound healing in diabetic (db/db) mice. VEGF-A₁₆₅ is a popular proangiogenic growth factor that stimulates multiple components in the wound-healing cascade. On the other hand, 11-MTA possesses antibacterial activity and can be bound to Au NPs easily through Au–S bonding. We have found that the surface density of VEGF-A₁₆₅ plays a vital role in promoting the proliferation, migration, and tube formation of human umbilical vein endothelial cells. 11-MTA tethered on the VEGF-modified Au NPs enables the nanocomposites (i.e., 11-MTA/VEGF-Au NPs) to exhibit a strong antimicrobial activity against multidrug-resistant bacteria [methicillin-resistant S. aureus (MRSA)]. The minimal inhibition concentration of 11-MTA/VEGF-Au NPs is ∼450-fold lower than that of 11-MTA, revealing their high antibacterial efficiency. 11-MTA/VEGF-Au NPs exhibit high biocompatibility. 11-MTA/VEGF-Au NPs as dressing materials to treat MRSA-infected wounds in diabetic mice not only show strong in vivo bactericidal activities but also enhance the healing process of the formation of collagen fibers and epithelialization. Our results show that dual-functional 11-MTA/VEGF-Au NPs are promising agents for clinical applications like treating chronic wound infections.

We have developed a rapid and straightforward topical treatment method for dry eye disease (DED) using poly(catechin) capped-gold nanoparticles (Au@Poly-CH NPs) carrying amfenac [AF; a nonsteroidal anti-inflammatory drug (NSAID)] through effective attenuation of ocular surface tissue damage in dry eyes. A dual-targeted strategy based on ocular therapeutics was adopted to simultaneously block the cyclooxygenase enzymes-induced inflammation and reactive oxygen species (ROS)-induced oxidative stress, the primary two causes of DED. The self-assembled core–shell Au@Poly-CH NPs synthesized via a simple reaction between tetrachloroaurate(III) and catechin possess a poly(catechin) shell (∼20 nm) on the surface of each Au NP (∼60 nm). The anti-oxidant and anti-inflammatory properties of AF/Au@Poly-CH NPs were evaluated by DCFH-DA and prostaglandin E2/VEGF assays, respectively. Our results demonstrate that Au@Poly-CH NPs not only act as an anti-oxidant to suppress ROS-mediated processes, but also serve as a drug carrier of AF for a synergistic effect on anti-inflammation. In vivo biocompatibility studies show good tolerability of AF/Au@Poly-CH NPs for potential use in the treatment of ocular surface pathologies. The dual-targeted therapeutic effects of AF/Au@Poly-CH NPs lead to rapid recovery from DED in a rabbit model. Au@Poly-CH NPs loaded with NSAIDs is a promising multifunctional nanocomposite for treating various inflammation- and oxidative stress-related diseases.

Complex antibacterial mechanisms of graphene oxide and carbon dots.

We have developed a simple and green solution for the synthesis of catalytic gold-doped bismuth oxyiodide (Au/BiOI) nanocomposites at room temperature from an aqueous mixture of gold ions, bismuth ions, and iodide ions. Au nanoparticles (NPs) were formed in situ and doped into BiOI nanosheets. The oxygen vacancies generated in BiOI give rise to its oxidase-like activity, and Au doping facilitated the reaction leading to a 4-fold higher oxidase-like activity of the Au/BiOI nanocomposite. The Au/BiOI nanocomposites showed wide spectrum antimicrobial activity not only against non-multidrug-resistant E. coli, K. pneumoniae, S. enteritidis, S. aureus, and B. subtilis bacteria, but also against multidrug-resistant bacteria, methicillin-resistant S. aureus (MRSA). The gold doping reduced the minimal inhibitory concentration value by ∼2000-fold for the Au/BiOI nanocomposite, in comparison with only BiOI nanoparticles. The bactericidal property of the Au/BiOI nanocomposite arose from the combined effect of the disruption of the bacterial membrane through a strong interaction of the nanocomposite with the bacteria and the generation of reactive oxygen species. Also, the Au/BiOI nanocomposite is highly biocompatible, which has been demonstrated in vitro by analysis of cytotoxicity and hemolysis, and in vivo by evaluating ocular tissue responses. Furthermore, intrastromal administration of Au/BiOI nanocomposites can effectively alleviate S. aureus-induced bacterial keratitis in rabbits, suggesting a significant disinfectant benefit in preclinical studies. The Au/BiOI nanocomposites show great potential for the inactivation of bacterial pathogens in an aqueous environment and treatment of bacterial infection-induced diseases.

Stereospecific recognition of chiral molecules is ubiquitous in chemical and biological systems, thus leading to strong demand for the development of enantiomeric drugs, enantioselective sensors, and asymmetric catalysts. In this study, we demonstrate the ratio of d-Cys and l-Cys playing an important role in determining the optical properties and the structures of self-assembled Cys–Au(I) supramolecules prepared through a simple reaction of tetrachloroaurate(III) with chiral cysteine (Cys). The irregularly shaped −[d-Cys–Au(I)]_n– or – [l-Cys–Au(I)]_n– supramolecules with a size larger than 500 nm possessing strong absorption in the near-UV region and chiroptical characteristics were only obtained from the reaction of Au(III) with d-Cys or l-Cys. On the other hand, spindle-shaped −[d/l-Cys–Au(I)]_n– supramolecules were formed when using Au(III) with mixtures of d/l-Cys. Our results have suggested that Au(I)···Au(I) aurophilic interactions, and stacked hydrogen bonding and zwitterionic interactions between d/l-Cys ligands are important in determining their structures. The NaBH₄-mediated reduction induces the formation of photoluminescent gold nanoclusters (Au NCs) embedded in the chiral −[d-Cys–Au(I)]_n– or −[l-Cys–Au(I)]_n– supramolecules with a quantum yield of ca. 10%. The as-formed Au NCs/–[d-Cys–Au(I)]_n– and Au NCs/–[l-Cys–Au(I)]_n– are an enantiospecific substrate that can trap l-carnitine and d-carnitine, respectively, and function as a nanomatrix for surface-assisted laser desorption/ionization mass spectrometry (LDI-MS). The high absorption efficiency of laser energy, analyte-binding capacity, and homogeneity of the Au NCs/–[Cys–Au(I)]_n– allow for quantitation of enantiomeric carnitine down to the micromolar regime with high reproducibility. The superior efficiency of the Au NCs/–[d-Cys–Au(I)]_n– substrate has been further validated by quantification of l-carnitine in dietary supplements with accuracy and precision. Our study has opened a new avenue for chiral quantitation of various analytes through LDI-MS using metal nanocomposites consisting of NCs and metal–ligand complexes.