Caging Cationic Polymer Brush-Coated Plasmonic Nanostructures for Traceable Selective Antimicrobial Activities.

Cationic polymers are under intense research to achieve prominent antimicrobial activity. However, the cellular and in vivo toxicity caused by nonspecific electrostatic interaction has become a major challenge for their practical applications. Here, the development of a "caging" strategy based on the use of a block copolymer consisting of a stealth block and an anionic block that undergoes degradation in presence of enzymes secreted by selective bacterial pathogens of interest is reported. The results have shown that antimicrobial cationic polymer brushes-coated gold nanorods (AuNRs) can be caged by the block polymer of poly(ethylene glycol) and anionic, lipase-degradable block of ε-caprolactone and methacrylic acid copolymer to afford neutrally charged surfaces. The caged AuNRs are activated by lipase released by bacteria of interest to endow an excellent bactericidal effect but show minimal binding and toxicity against mammalian cells and nonspecific bacteria that do not produce lipase. In this design, AuNRs play multifunctional roles as the scaffolds for polymer brushes, photothermal transducers, and imaging probes for traceable delivery of the activation and delivery of bactericidal cationic polymer brushes. The caging strategy opens new opportunities for the safe delivery of antimicrobial materials for the treatment of bacterial infections.

Antibiofilm Activity of Gallium(III) Complexed Anionic Polymers in Combination with Antibiotics.

Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening pathogen associated with multiantibiotic resistance, which is largely caused by its strong ability to form biofilms. Recent research has revealed that gallium (III) shows an activity against the biofilm of P. aeruginosa by interfering with Fe metabolism. The antibacterial activity of the combination of Ga3+ ion and antibiotic rifampicin (RMP) against P. aeruginosa PAO1 is investigated. An anionic polymer poly{{2-[(2-methylprop-2-enoyl)oxy]ethyl}phosphonic acid} (PDMPOH) is exploited to form complexes (GaPD) with Ga3+ . The GaPD complexes act as a carrier of Ga3+ and release Ga3+ via enzymatic degradation by bacterial lipases. GaPD is found to damage the outer membrane, leading to enhanced cellular uptake of RMP and Ga3+ due to increased outer membrane permeability, which inhibits the RNA polymerase and interferes with Fe metabolism. The antibiofilm activity and biocompatibility of the GaPD system offer a promising treatment option for P. aeruginosa biofilm-related infections.

Identification of ssDNA aptamers specific to clinical isolates of Streptococcus mutans strains with different cariogenicity.

Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries.

Mechano-triggered eradication of dentinal tubule biofilm via in situ generation of nanoscale sonosensitizer by the tailored irrigation formulation.

The efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H2O2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H2O2 and Fc liberated Fe3+ that was further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential.

The Intrinsic Relation between the Hydrogel Structure and In Vivo Performance of Hyaluronic Acid Dermal Fillers: A Comparative Study of Four Typical Dermal Fillers.

BACKGROUND: Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough. METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism. RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juvéderm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juvéderm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. CONCLUSION: It's necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.

Formation of PdPt alloy nanodots on gold nanorods: tuning oxidase-like activities via composition.

The island growth mode of Pt was employed to guide the forma-tion of PdPt alloy nanodots on gold nanorods (Au@PdPt NRs). Well-defined alloy nanodots, with tunable Pd/Pt ratios from 0.2 to 5, distribute homogeneously on the surface of the Au NR. Formation of nanodots shell leads to the red-shift and broadening of the longitudinal surface plasmon resonance (LSPR) band of the Au NRs. The Au@PdPt alloy NRs exhibit catalytic activity toward oxidation of often-used chromogenic substrates by dissolved oxygen under mild conditions, suggesting a new type of oxidase mimics. Composition dependence catalytic activity is observed for the oxidation of ascorbic acid (AA) and 3,3',5,5'-tetramethylbenzidine (TMB) and for the reduction of p-nitrophenol. For AA and TMB, catalytic activity enhances quickly at lower Pd/Pt ratios and tends to saturate at higher Pd/Pt ratios. For p-nitrophenol reduction, catalytic activity shows a nice linear relationship with Pd/Pt ratio owing to much higher catalytic activity of Pd. In conclusion, proper alloying of Pd and Pt presents an effective route to tailor the catalytic activity. Interesting, alloy nanodots can also catalyze the oxidation of Fe (II) to Fe (III) by dissolved oxygen. Thus, based on the competitive oxidation of TMB and Fe (II), selective detection of the latter can be achieved.

A Self-Assembled Plasmonic Substrate for Enhanced Fluorescence Resonance Energy Transfer.

Fluorescence resonance energy transfer (FRET) has found widespread uses in biosensing, molecular imaging, and light harvesting. Plasmonic metal nanostructures offer the possibility of engineering photonic environment of specific fluorophores to enhance the FRET efficiency. However, the potential of plasmonic nanostructures to enable tailored FRET enhancement on planar substrates remains largely unrealized, which are of considerable interest for high-performance on-surface bioassays and photovoltaics. The main challenge lies in the necessitated concurrent control over the spectral properties of plasmonic substrates to match that of fluorophores and the fluorophore-substrate spacing. Here, a self-assembled plasmonic substrate based on polydopamine (PDA)-coated plasmonic nanocrystals is developed to effectively address this challenge. The PDA coating not only drives interfacial self-assembly of the nanocrystals to form closely packed arrays with customized optical properties, but also can serve as a tailored nanoscale spacer between the fluorophores and plasmonic nanocrystals, which collectively lead to optimized fluorescence enhancement. The biocompatible plasmonic substrate that allows convenient bioconjugation imparted by PDA has afforded improved FRET efficiency in DNA microarray assay and FRET imaging of live cells. It is envisioned that the self-assembled plasmonic substrates can be readily integrated into fluorescence-based platforms for diverse biomedical and photoconversion applications.

Mesoporous polydopamine with built-in plasmonic core: Traceable and NIR triggered delivery of functional proteins.

Functional proteins are essential for the regulation of cellular behaviors and have found growing therapeutic uses. However, low bioavailability of active proteins to their intracellular targets has been a long-standing challenge to achieve their full potential for cell reprogramming and disease treatment. Here we report mesoporous polydopamine (mPDA) with a built-in plasmonic nanoparticle core as a multifunctional protein delivery system. The mPDA with a unique combination of large surface area, metal-chelating property, and broad-spectrum photothermal transduction allows efficient loading and near-infrared light-triggered release of functional proteins, while the plasmonic core serves as a photostable tracer and fluorescence quencher, collectively leading to real-time monitoring and active cytosolic release of model proteins. In particular, controlled delivery of cytotoxic ribonuclease A has shown excellent performance in invivo cancer therapy. The possibility of coating mPDA on a broad range of functional cores, thanks to its universal adhesion, provides opportunities for developing tailored delivery carriers of biologics to overcome intrinsic biological barriers.

Surface modification of titanium with hydroxyapatite layer induced by phase-transited lysozyme coating.

Surface modification of titanium with a hydroxyapatite (HAP) coating can improve the bioactivity of pristine titanium. The traditional techniques for coating HAP on titanium involve nonmild treatments using strong bases or acids or high temperatures. In this study, the coating of HAP was carried out by a novel methodology called phase-transited lysozyme-assisted hydroxyapatite formation (PAH); in this process of biomimetic mineralization, the abundant functional carboxyl groups of phase-transited lysozyme (PTL) were responsible for the nucleation of HAP crystals by concentrating Ca2+ ions at the interface between PTL and CaCl2 solution and for the subsequent growth of HAP crystals occurring in simulated body fluid (SBF). In vitro and in vivo experiments verified that the surface of titanium modified with the HAP/PTL-Ti multilayer was endowed with improved biocompatibility and osteoinductivity compared with those of pristine titanium. Therefore, PAH is a simple, rapid, low-cost and green process for the surface modification of titanium with an HAP coating and thus will be a promising methodology for the surface modification of titanium implants.

Raman-encoded, multivalent glycan-nanoconjugates for traceable specific binding and killing of bacteria.

Glycan recognition plays key roles in cell-cell and host-pathogen interactions, stimulating widespread interest in developing multivalent glycoconjugates with superior binding affinity for biological and medical uses. Here, we explore the use of Raman-encoded silver coated gold nanorods (GNRs) as scaffolds to form multivalent glycoconjugates. The plasmonic scaffolds afford high-loading of glycan density and their optical properties offer the possibilities of monitoring and quantitative analysis of glycan recognition. Using E. coli strains with tailored on/off of the FimH receptors, we have demonstrated that Raman-encoded GNRs not only allow for real-time imaging and spectroscopic detection of specific binding of the glycan-GNR conjugates with bacteria of interest, but also cause rapid eradication of the bacteria due to the efficient photothermal conversion of GNRs in the near-infrared spectral window. We envision that optically active plasmonic glycoconjugates hold great potential for screening multivalent glycan ligands for therapeutic and diagnostic applications.

Compact Plasmonic Blackbody for Cancer Theranosis in the Near-Infrared II Window.

We have developed a class of blackbody materials, i. e., hyperbranched Au plasmonic blackbodies (AuPBs), of compact sizes (<50 nm). The AuPBs were prepared in a seedless and surfactant-free approach based on the use of mussel-inspired dopamine. Strong intraparticle plasmonic coupling among branches in close proximity leads to intense and uniform broadband absorption across 400-1350 nm. The blackbody absorption imparts the compact AuPB with a superior photothermal efficiency of >80% and closely matched photothermal activity in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) spectral windows, making it a rare broadband theranostic probe for integrated photoacoustic imaging and photothermal therapy (PTT). Our comparative study, using the same probe, has demonstrated that the improved PTT outcome of NIR-II over NIR-I primarily results from its higher maximum permission exposure (MPE) rather than the deeper tissue penetration favored by longer wavelengths. The compact plasmonic broadband nanoabsorbers with tailored surface properties hold potential for a wide spectrum of light-mediated applications.