Cocktail Approach with Polyserotonin Nanoparticles and Peptides for Treatment of Streptococcus mutans.

Dental plaque, formed by a Streptococcus mutans biofilm, is a major contributor to cavity formation. While antimicrobial strategies exist, the growing risk of antibiotic resistance necessitates alternative therapeutic solutions. Polyserotonin nanoparticles (PSeNPs), recently recognized for their photothermal property and promising biomedical applications, open up a new avenue for antimicrobial use. Here, we introduced a UV-initiated synthetic route for PSeNPs with improved yield. Using these PSeNPs, a cocktail treatment to reduce the viability of this cavity-causing bacteria was developed. This cocktail comprises an S. mutans-targeting antimicrobial peptide (GH12), an intraspecies competence-stimulating peptide that triggers altruistic cell death in S. mutans, and laser-activated heating of PSeNPs. The "peptide + PSeNP + laser" combination effectively inhibits S. mutans growth in both planktonic and biofilm states. Moreover, the cocktail approach remains effective in reducing the viability of S. mutans in a more virulent dual-species biofilm with Candida albicans. Overall, our results reinforce the utility of a multipronged therapeutic strategy to reduce cariogenic bacteria in the complex model oral biofilm.

Different drug loading methods and antibiotic structure modulate the efficacy of polydopamine nanoparticles as drug nanocarriers.

The inefficient delivery of antimicrobials to their target is a significant factor contributing to antibiotic resistance. As such, smart nanomaterials that respond to external stimuli are extensively explored for precise drug delivery. Here, we investigate how drug loading methods and the structure of antibiotics impact the effectiveness of photothermally active polydopamine nanoparticles (PDNPs) as a laser-responsive drug delivery system. We examine two loading methods: in-synthesis and post-synthesis, and evaluate how laser irradiation affects drug release. Density functional theory calculations are also performed to gain deeper insights into the drug-PDNP interactions. Our findings point to the critical role of antibiotic structure and drug loading method in the laser-responsive capabilities of PDNPs as drug nanocarriers. Our study offers valuable insights for optimizing the design and efficiency of PDNP-based drug delivery systems.

Laser-responsive sequential delivery of multiple antimicrobials using nanocomposite hydrogels.

Precise control of antimicrobial delivery can prevent the adverse effects of antibiotics. By exploiting the photothermal activity of polydopamine nanoparticles along with the distinct transition temperatures of liposomes, a near-infrared (NIR) laser can be used to control the sequential delivery of an antibiotic and its adjuvant from a nanocomposite hydrogel-preventing bacterial growth.

Buffer Components Incorporate into the Framework of Polyserotonin Nanoparticles and Films during Synthesis.

Polyserotonin nanoparticles (PSeNP) and films are bioinspired nanomaterials that have potential in biomedical applications and surface coatings. As studies on polyserotonin (PSe) nanoparticles and films are still in their infancy, synthetic pathways and material development for this new class of nanomaterial await investigation. Here, we sought to determine how different buffers used during the polymerization of serotonin to form nanoparticles and films impact the physicochemical properties of PSe materials. We show that buffer components are incorporated into the polymer matrix, which is also supported by density functional theory calculations. While we observed no significant differences between the elasticity of nanoparticles synthesized in the different buffers, the nanoscale surface properties of PSe films revealed dissimilarities in surface functional groups influenced by solvent molecules. Overall, the results obtained in this work can be used towards the rational design of PSe nanomaterials with tailored properties and for specific applications.

Polyacrylamide hydrogels doped with different shapes of silver nanoparticles: Antibacterial and mechanical properties.

The incorporation of nanoparticles into a hydrogel matrix enables the development of innovative smart materials with enhanced biophysical properties. In this proof-of-concept study, we encapsulated different shapes (spherical, triangular and rod) of silver nanoparticles (AgNPs) within a hydrogel matrix of polyacrylamide (PAA) and N-methylenebisacrylamide (MBA) (PAA-MBA) to investigate whether these hydrogels exhibited shape-dependent antimicrobial and mechanical properties. We examined the mechanism of adsorption of different shapes of AgNPs using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Results showed that the adsorption of AgNPs was primarily occurring on the surface/outer pores of the PAA-MBA hydrogel and that rod AgNPs demonstrated a relatively slower adsorption within the hydrogel matrix. The mechanical properties of AgNP-doped hydrogels were evaluated using rheology and atomic force microscopy (AFM) quantitative imaging. We observed a higher storage and Young's modulus which proved that the incorporation of the various shapes of AgNPs increased the mechanical properties of the hydrogels with no significant differences between the different shapes. While both spherical and triangular AgNP-doped hydrogels showed strong antimicrobial activity, the hydrogel with the rod AgNPs had a relatively lower antimicrobial activity. Overall, our preliminary results demonstrated that nanocomposite hydrogels were promising materials for applications in the future development of wound dressings.

Size-controlled synthesis of bioinspired polyserotonin nanoparticles with free radical scavenging activity.

Polyserotonin-based nanoparticles are a new class of bioinspired nanomaterial with recently demonstrated therapeutic potential for future clinical applications. It is therefore important to establish a robust and rapid method of synthesizing polyserotonin nanoparticles (PSeNP) in the size range ideal for in vivo utilization. Since the formation of PSeNP is base-catalyzed, here we report the influence of solution pH, in the presence of different base systems, on the kinetics of PSeNP formation and physico-chemical properties of the resulting nanoparticles. We show that the rate of formation and the size of PSeNP depend on both the nature of the base and the initial pH of the reaction. We have also improved the kinetics of particle formation by performing the synthesis at an elevated temperature (60 °C), leading to a dramatic reduction in synthesis time from days to hours. This presents a significant advance in the efficiency of PSeNP synthesis and provides a facile approach in tuning the size of nanoparticles to suit various applications. Furthermore, we show that similar to serotonin, PSeNP also exhibits free radical scavenging property. Our results demonstrate that PSeNP has the potential to become a key player in the advancement of nanotechnology-mediated antioxidative therapy.

Plasmon-Mediated Drilling in Thin Metallic Nanostructures.

Thin and ultraflat conductive surfaces are of particular interest to use as substrates for tip-enhanced spectroscopy applications. Tip-enhanced spectroscopy exploits the excitation of a localized surface plasmon resonance mode at the apex of a metallized atomic force microscope tip, confining and enhancing the local electromagnetic field by several orders of magnitude. This allows for nanoscale mapping of the surface with high spatial resolution and surface sensitivity, as demonstrated when coupled to local Raman measurements. In gap-mode tip-enhanced spectroscopy, the specimen of interest is deposited onto a flat metallic surface and probed by a metallic tip, allowing for further electromagnetic confinement and subsequent enhancement. We investigate here a geometry where a gold tip is used in conjunction with a silver nanoplate, thus forming a heterometallic platform for local enhancement. When irradiated, a plasmon-mediated reaction is triggered at the tip-substrate junction due to the enhanced electric field and the transfer of hot electrons from the tip to the nanoplate. This resulting nanoscale reaction appears to be sufficient to ablate the thin silver plates even under weak laser intensity. Such an approach may be further exploited for patterning metallic nanostructures or photoinduced chemical reactions at metal surfaces.