Nanomaterials for Photothermal Antimicrobial Surfaces.

Microbial infection diseases are a major threat to human health and have become one of the main causes of mortality. The search for novel antimicrobial strategies is an important challenge for the scientific community, considering also the constant increase of antimicrobial resistance and the rise of new diseases. Among the new strategies to combat microbial infections, the photothermal effect seems to be one of the most promising. Hyperthermia is an effective and broad spectrum strategy for the removal of microbial infections. Among all of the strategies to reduce the diffusion of microbial infections, the preparation of antimicrobial surfaces seems of primary importance. In many cases, in fact, an infection can be diffused through surfaces just by touching them, or by inoculating microbes through an internalizable device, such as an implant, a prosthesis, or a catheter. In this review, we will summarize the recent advances in the preparation of photothermal antibacterial surfaces.

Thiolated Cyanines Appended to Partially Pegylated Gold Nanoparticles for Fluorescence Quenching of Two-Channel Photothermal Inks.

Following a new approach, we prepared a nanoink with two separate photothermally responsive absorption bands. One is the localized surface plasmon resonance (LSPR) absorption of gold nanoparticles (AuNP, d =17 nm), the second is the absorption band of two cyanine (Cy) dyes, Cy7-C6 or Cy7-C11, grafted to the AuNP surface through thiolated bridges of different lengths: the close proximity to the Au surface induces full quenching of the Cy fluorescence, resulting in thermal relaxation on irradiation. Attempts to full coat AuNP with the lipophilic Cy7-C6 and Cy7-C11 lead to precipitation from aqueous solutions. We thus prepared AuNP with partial pegylation (30, 50, or 70%), using a long chain thiol-terminated PEG bearing a -COOH function. Addition until saturation of either Cy7-C6 or Cy7-C11 to the partially pegylated AuNP gave the AuNP@Cy/PEGX% hybrids (X = 30, 50, 70) that are stable in water and in the water/alcohol mixtures used to prepare the nanoinks. Further overcoating of AuNP@Cy7-C6/PEG50% with PAH (polyallylamine hydrochloride) avoids LSPR hybridization in the dry nanoink printouts, that present two separate bands. When irradiated with laser sources near their absorption maxima, the printouts of the AuNP@Cy7-C6/PEG50%@PAH nanoink respond on two channels, giving different temperature increases depending on the irradiation wavelength.

Enhanced in vitro immersion behavior and antibacterial activity of NiTi orthopedic biomaterial by HAp-Nb2O5 composite deposits.

NiTi is a class of metallic biomaterials, benefit from superelastic behavior, high biocompatibility, and favorable mechanical properties close to that of bone. However, the Ni ion leaching, poor bioactivity, and antibacterial activity limit its clinical applications. In this study, HAp-Nb2O5 composite layers were PC electrodeposited from aqueous electrolytes containing different concentrations of the Nb2O5 particles, i.e., 0-1 g/L, to evaluate the influence of the applied surface engineering strategy on in vitro immersion behavior, Ni2+ ion leaching level, and antibacterial activity of the bare NiTi. Surface characteristics of the electrodeposited layers were analyzed using SEM, TEM, XPS, and AFM. The immersion behavior of the samples was comprehensively investigated through SBF and long-term PBS soaking. Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) infective reference bacteria were employed to address the antibacterial activity of the samples. The results illustrated that the included particles led to more compact and smoother layers. Unlike bare NiTi, composite layers stimulated apatite formation upon immersion in both SBF and PBS media. The concentration of the released Ni2+ ion from the composite layer, containing 0.50 g/L Nb2O5 was ≈ 60% less than that of bare NiTi within 30 days of immersion in the corrosive PBS solution. The Nb2O5-reinforced layers exhibited high anti-adhesive activity against both types of pathogenic bacteria. The hybrid metallic-ceramic system comprising HAp-Nb2O5-coated NiTi offers the prospect of a potential solution for clinical challenges facing the orthopedic application of NiTi.

Prussian Blue nanoparticles: An FDA-approved substance that may quickly degrade at physiological pH.

Prussian blue (PB) is a coordination polymer based on the Fe2+…CN…Fe3+ sequence. It is an FDA-approved drug, intended for oral use at the acidic pH of the stomach and of most of the intestine track. However, based on FDA approval, a huge number of papers proposed the use of PB nanoparticles (PBnp) under "physiological conditions", meaning pH buffered at 7.4 and high saline concentration. While most of these papers report that PBnp are stable at this pH, a small number of papers describes instead PBnp degradation at the same or similar pH values, i.e. in the 7-8 range. Here we give a definitively clear picture: PBnp are intrinsically unstable at pH ≥ 7, degrading with the fast disappearance of their 700 nm absorption band, due to the formation of OH- complexes from the labile Fe3+ centers. However, we show also that the presence of a polymeric coating (PVP) can protect PBnp at pH 7.4 for over 24 h. Moreover, we demonstrate that when "physiological conditions" include serum, a protein corona is rapidly formed on PBnp, efficiently avoiding degradation. We also show that the viability of PBnp-treated EA.hy926, NCI-H1299, and A549 cells is not affected in a wide range of conditions that either prevent or promote PBnp degradation.

Dual mode antibacterial surfaces based on Prussian blue and silver nanoparticles.

Prussian Blue (PB) is an inexpensive, biocompatible, photothermally active material. In this paper, self-assembled monolayers of PB nanoparticles were grafted on a glass surface, protected with a thin layer of silica and decorated with spherical silver nanoparticles. This combination of a photothermally active nanomaterial, PB, and an intrinsically antibacterial one, silver, leads to a versatile coating that can be used for medical devices and implants. The intrinsic antibacterial action of nanosilver, always active over time, can be enhanced on demand by switching on the photothermal effect of PB using near infrared (NIR) radiation, which has a good penetration depth through tissues and low side effects. Glass surfaces functionalized by this layer-by-layer approach have been characterized for their morphology and composition, and their intrinsic and photothermal antibacterial effect was studied against Gram+ and Gram- planktonic bacteria.

Surface-Enhanced Raman Spectroscopy Chips Based on Silver Coated Gold Nanostars.

Surface-enhanced Raman scattering (SERS) is becoming widely used as an analytical tool, and the search for stable and highly responsive SERS substrates able to give ultralow detection of pollutants is a current challenge. In this paper we boosted the SERS response of Gold nanostars (GNS) demonstrating that their coating with a layer of silver having a proper thickness produces a 7-fold increase in SERS signals. Glass supported monolayers of these GNS@Ag were then prepared using simple alcoxyliane chemistry, yielding efficient and reproducible SERS chips, which were tested for the detection of molecules representative of different classes of pollutants. Among them, norfloxacin was detected down to 3 ppb, which is one of the lowest limits of detection obtained with this technique for the analyte.

A Supramolecular Approach to Antimicrobial Surfaces.

In this paper, we report on the preparation of Imidazole-functionalized glass surfaces, demonstrating the ability of a dinuclear Cu(II) complex of a macrocyclic ligand to give a "cascade" interaction with the deprotonated forms of grafted imidazole moieties. In this way, we realized a prototypal example of an antimicrobial surface based on a supramolecular approach, obtaining a neat microbicidal effect using low amounts of the described copper complex.

Gold Nanoparticles Contact with Cancer Cell: A Brief Update.

The fine-tuning of the physicochemical properties of gold nanoparticles has facilitated the rapid development of multifunctional gold-based nanomaterials with diagnostic, therapeutic, and therapeutic applications. Work on gold nanoparticles is increasingly focusing on their cancer application. This review provides a summary of the main biological effects exerted by gold nanoparticles on cancer cells and highlights some critical factors involved in the interaction process (protein corona, tumor microenvironment, surface functionalization). The review also contains a brief discussion of the application of gold nanoparticles in target discovery.

Gold Nanostars Embedded in PDMS Films: A Photothermal Material for Antibacterial Applications.

Bacteria infections and related biofilms growth on surfaces of medical devices are a serious threat to human health. Controlled hyperthermia caused by photothermal effects can be used to kill bacteria and counteract biofilms formation. Embedding of plasmonic nano-objects like gold nanostars (GNS), able to give an intense photothermal effect when irradiated in the NIR, can be a smart way to functionalize a transparent and biocompatible material like polydimethylsiloxane (PDMS). This process enables bacteria destruction on surfaces of PDMS-made medical surfaces, an action which, in principle, can also be exploited in subcutaneous devices. We prepared stable and reproducible thin PDMS films containing controllable quantities of GNS, enabling a temperature increase that can reach more than 40 degrees. The hyperthermia exerted by this hybrid material generates an effective thermal microbicidal effect, killing bacteria with a near infrared (NIR) laser source with irradiance values that are safe for skin.

Nanocomposite Sprayed Films with Photo-Thermal Properties for Remote Bacteria Eradication.

Currently there is a strong demand for novel protective materials with efficient antibacterial properties. Nanocomposite materials loaded with photo-thermally active nanoparticles can offer promising opportunities due to the local increase of temperature upon near-infrared (NIR) light exposure capable of eradicating bacteria. In this work, we fabricated antibacterial films obtained by spraying on glass slides aqueous solutions of polymers, containing highly photo-thermally active gold nanostars (GNS) or Prussian Blue (PB) nanoparticles. Under NIR light irradiation with low intensities (0.35 W/cm2) these films demonstrated a pronounced photo-thermal effect: ΔTmax up to 26.4 °C for the GNS-containing films and ΔTmax up to 45.8 °C for the PB-containing films. In the latter case, such a local temperature increase demonstrated a remarkable effect on a Gram-negative strain (P. aeruginosa) killing (84% of dead bacteria), and a promising effect on a Gram-positive strain (S. aureus) eradication (69% of dead bacteria). The fabricated films are promising prototypes for further development of lightweight surfaces with efficient antibacterial action that can be remotely activated on demand.

Self-Assembled Monolayers of Copper Sulfide Nanoparticles on Glass as Antibacterial Coatings.

We developed an easy and reproducible synthetic method to graft a monolayer of copper sulfide nanoparticles (CuS NP) on glass and exploited their particular antibacterial features. Samples were fully characterized showing a good stability, a neat photo-thermal effect when irradiated in the Near InfraRed (NIR) region (in the so called "biological window"), and the ability to release controlled quantities of copper in water. The desired antibacterial activity is thus based on two different mechanisms: (i) slow and sustained copper release from CuS NP-glass samples, (ii) local temperature increase caused by a photo-thermal effect under NIR laser irradiation of CuS NP-glass samples. This behavior allows promising in vivo applications to be foreseen, ensuring a "static" antibacterial protection tailored to fight bacterial adhesion in the critical timescale of possible infection and biofilm formation. This can be reinforced, when needed, by a photo-thermal action switchable on demand by an NIR light.

Fast dissolution of silver nanoparticles at physiological pH.

While silver nanoparticles (AgNP) are used in topical treatments and medical devices for humans, no smooth, safe remedy exists to remove them and avoid possible post-treatment uptake in the body. We show here that cysteamine hydrochloride (CYS∙HCl), a simple FDA and EMA approved molecule, is able to dramatically accelerate the otherwise extremely slow oxidation of citrate-coated AgNP by O2 in a wide range of pH, including the physiological 7.4 value, obtaining the halving of AgNP concentration in t < 10 min. The dependence of oxidation kinetics on CYS concentration and pH is studied, finding faster processes on increasing CYS and basicity, despite the decrease of O2 reduction potential. Complexation and electrochemical studies demonstrate that CYS adhesion to AgNP surface followed by formation of 1:2 Ag+:CYS complex is the driving force for the AgNP oxidation, this also giving a definitive explanation to the otherwise still unclear phenomenon of AgNP etching by thiols. The efficacy of CYS∙HCl is verified also on AgNP coated with pectin and PEG-SH, and on AgNP immobilized on surfaces.

High Stability Thiol-Coated Gold Nanostars Monolayers with Photo-Thermal Antibacterial Activity and Wettability Control.

The adhesion and proliferation of bacteria on abiotic surfaces pose challenges in both health care and industrial applications. Gold nanostars (GNSs) monolayers grafted on glass have demonstrated to exert antibacterial action due to their photo-thermal features. Here, these GNS layers were further functionalized using thiols monolayers, in order to impart different wettability to the surfaces and thus adding a feature that could help to fight bacterial proliferation. Thiol that has different functional groups was used and the thiol-protected surfaces were characterized by means of UV-vis spectroscopy, contact angles, SEM and surface enhanced Raman spectroscopy (SERS). We verified that (i) coating with the proper thiol allows us to impart high hydrophilicity or hydrophobicity to the surfaces (with contact angle values ranging from 10 to 120°); (ii) GNS monolayers are strongly stabilized by functionalization with thiols, with shelf stability increasing from a few weeks to more than three months and (iii) photo-thermal features and subsequent antibacterial effects caused by hyperthermia are not changed by thiols layers, allowing us to kill at least 99.99% of representative bacterial strains.

Chitosan Oleate Coated Poly Lactic-Glycolic Acid (PLGA) Nanoparticles versus Chitosan Oleate Self-Assembled Polymeric Micelles, Loaded with Resveratrol.

Chitosan oleate (CS-OA), a chitosan salt with amphiphilic properties, has demonstrated the ability to self-assemble in aqueous environment to give polymeric micelles useful to load poorly soluble drugs. More recently, CS-OA was proposed to stabilize nanoemulsions during the preparation by emulsification and solvent evaporation of poly lactic-glycolic acid (PLGA) nanoparticles (NPs) loaded with curcumin. Positive mucoadhesive behavior and internalization properties were demonstrated for these NPs attributable to the presence of positive charge at the NP surface. In the present paper, two CS-OA-based nanosystems, micelles and PLGA NPs, were compared with the aim of elucidating their physico-chemical characteristics, and especially their interaction with cell substrates. The two systems were loaded with resveratrol (RSV), a hydrophobic polyphenol endowed with anti-cancerogenic, anti-inflammatory, and heart/brain protective effects, but with low bioavailability mainly due to poor aqueous solubility. Calorimetric analysis and X-ray spectra demonstrated amorphization of RSV, confirming its affinity for hydrophobic domains of polymeric micelles and PLGA core of NPs. TGA decomposition patterns suggest higher stability of PLGA-NPs compared with polymeric micelles, that anyway resulted more stable than expected, considering the RSV release profiles, and the cell line interaction results.

High Bactericidal Self-Assembled Nano-Monolayer of Silver Sulfadiazine on Hydroxylated Material Surfaces.

Anti-infective surfaces are a modern strategy to address the issue of infection related to the clinical use of materials for implants and medical devices. Nanocoatings, with their high surface/mass ratio, lend themselves to being mono-layered on the material surfaces to release antibacterial molecules and prevent bacterial adhesion. Here, a "layer-by-layer" (LbL) approach to achieve a self-assembled monolayer (SAM) with high microbicidal effect on hydroxylated surfaces is presented, exploiting the reaction between a monolayer of thiolic functions on glass/quartz surfaces and a newly synthesized derivative of the well-known antibacterial compound silver sulfadiazine. Using several different techniques, it is demonstrated that a nano-monolayer of silver sulfadiazine is formed on the surfaces. The surface-functionalized materials showed efficient bactericidal effect against both Gram-positive and Gram-negative bacteria. Interestingly, bactericidal self-assembled nano-monolayers of silver sulfadiazine could be achieved on a large variety of materials by simply pre-depositing glass-like SiO2 films on their surfaces.

Novel photo-thermally active polyvinyl alcohol-Prussian blue nanoparticles hydrogel films capable of eradicating bacteria and mitigating biofilms.

Antibacterial treatment is an essential issue in many diverse fields, from medical device treatments (for example prostheses coating) to food preservation. However, there is a need of novel and light-weight materials with high antibacterial efficiency (preferably due to the physical activation). Utilization of photo-thermally active nanoparticles can lead to novel and re-usable materials that can be remotely activated on-demand to thermally eradicate bacteria and mitigate biofilm formation, therefore meeting the above challenge. In this study polyvinyl alcohol (PVA) hydrogel films containing non-toxic and highly photo-thermally active Prussian blue (PB) nanoparticles were fabricated. The confocal microscopy studies indicated a uniform nanoparticle distribution and a low degree of aggregation. Upon near-infrared (NIR; 700 and 800 nm) light irradiation of PVA-PB films, the local temperature increases rapidly and reaches a plateau (up to ΔT â‰… 78 °C), within ≈6-10 s under relatively low laser intensities, I â‰… 0.3 W cm-2. The high and localized increase of temperature on the fabricated films resulted in an efficient antibacterial effect on Pseudomonas aeruginosa (P. aeruginosa) bacteria. In addition, the localized photo-thermal effect was also sufficient to substantially mitigate biofilms growth.

Prussian Blue Nanoparticles as a Versatile Photothermal Tool.

Prussian blue (PB) is a coordination polymer studied since the early 18th century, historically known as a pigment. PB can be prepared in colloidal form with a straightforward synthesis. It has a strong charge-transfer absorption centered at ~700 nm, with a large tail in the Near-IR range. Irradiation of this band results in thermal relaxation and can be exploited to generate a local hyperthermia by irradiating in the so-called bio-transparent Near-IR window. PB nanoparticles are fully biocompatible (PB has already been approved by FDA) and biodegradable, this making them ideal candidates for in vivo use. While papers based on the imaging, drug-delivery and absorbing properties of PB nanoparticles have appeared and have been reviewed in the past decades, a very recent interest is flourishing with the use of PB nanoparticles as photothermal agents in biomedical applications. This review summarizes the syntheses and the optical features of PB nanoparticles in relation to their photothermal use and describes the state of the art of PB nanoparticles as photothermal agents, also in combination with diagnostic techniques.

Synthesis of reduced-size gold nanostars and internalization in SH-SY5Y cells.

The synthesis of large pentatwinned five-branched gold nanostars (GNS) has been modified so to obtain overall dimensions shrunk to 60% and a lower branches aspect ratio, leading to a dramatic blue shift of their two near-infrared (NIR) localized surface plasmon resonances (LSPR) absorptions but still maintaining one LSPR in the biotransparent NIR range. The interactions of polyethylene glycol (PEG) coated large and shrunk GNS with SH-SY5Y cells revealed that the large ones (DCI - diameter of the circumference in which GNS can be inscribed=76nm) are internalized more efficiently than the shrunk ones (DCI=46nm), correlating with a decreased cells surviving fraction.

Modular approach for bimodal antibacterial surfaces combining photo-switchable activity and sustained biocidal release.

Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects.

Bulk Surfaces Coated with Triangular Silver Nanoplates: Antibacterial Action Based on Silver Release and Photo-Thermal Effect.

A layer of silver nanoplates, specifically synthesized with the desired localized surface plasmon resonance (LSPR) features, was grafted on amino-functionalized bulk glass surfaces to impart a double antibacterial action: (i) the well-known, long-term antibacterial effect based on the release of Ag⁺; (ii) an "on demand" action which can be switched on by the use of photo-thermal properties of silver nano-objects. Irradiation of these samples with a laser having a wavelength falling into the so called "therapeutic window" of the near infrared region allows the reinforcement, in the timescale of minutes, of the classical antibacterial effect of silver nanoparticles. We demonstrate how using the two actions allows for almost complete elimination of the population of two bacterial strains of representative Gram-positive and Gram-negative bacteria.