Photothermal nanoparticles for ablation of bacteria associated with kidney stones.

OBJECTIVE: To determine whether photothermal polymer nanoparticles (NPs) can interface with bacteria associated with kidney stones, generate heat when stimulated with near infrared (NIR) light, and aid in reducing bacterial burden. METHODS: Two types of kidney stones, artificial, and those removed during percutaneous nephrolithotomy (PCNL), were inoculated with Escherichia coli (E. coli) and then incubated with NPs composed of FITC-labeled Poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']-dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). Association of the PCPDTBSe NPs was evaluated using fluorescence microscopy. Infected stones were incubated with NPs and exposed to 800 nm light to generate temperature increases from 25.4 to 68.6 °C on the stones. Following photothermal treatment, the stones were homogenized and the bacteria was enumerated via colony counting assays to evaluate the bactericidal effect. The photothermal effect was also evaluated using scanning electron microscopy of the treated biofilms. RESULTS: Both kidney stone types sequestered E. coli. Control stones and stones treated with laser only had growth of numerous bacterial colonies, while stones exposed to NPs and laser grew significantly less, or none (p = 0.02). CONCLUSIONS: The polymer NPs interface with E. coli on artificial and patient-derived kidney stones, and they can impart a bactericidal effect, when stimulated with NIR to generate heat. This technique may possibly be extended to treating infected kidney stones in patients.

Bio-assisted synthesis of bimetallic nanoparticles featuring antibacterial and photothermal properties for the removal of biofilms.

Biofilms are responsible for about considerable amounts of cases of bacterial infections in humans. They are considered a major threat to transplant and chronic wounds patients due to their highly resistant nature against antibacterial materials and due to the limited types of techniques that can be applied to remove them. Here we demonstrate a successful in-situ bio-assisted synthesis of dual functionality nanoparticles composed of Silver and Gold. This is done using a jellyfish-based scaffold, an antibacterial material as the templating host in the synthesis. We further explore the scaffold's antibacterial and photothermal properties against various gram-negative and positive model bacteria with and without photo-induced heating at the Near-IR regime. We show that when the scaffold is loaded with these bimetallic nanoparticles, it exhibits dual functionality: Its photothermal capabilities help to disrupt and remove bacterial colonies and mature biofilms, and its antibacterial properties prevent the regrowth of new biofilms.

Thermo-resistance of ESKAPE-panel pathogens, eradication and growth prevention of an infectious biofilm by photothermal, polydopamine-nanoparticles in vitro.

Nanotechnology offers many novel infection-control strategies that may help prevent and treat antimicrobial-resistant bacterial infections. Here, we synthesized polydopamine, photothermal-nanoparticles (PDA-NPs) without further surface-functionalization to evaluate their potential with respect to biofilm-control. Most ESKAPE-panel pathogens in suspension with photothermal-nanoparticles showed three- to four-log-unit reductions upon Near-Infra-Red (NIR)-irradiation, but for enterococci only less than two-log unit reduction was observed. Exposure of existing Staphylococcus aureus biofilms to photothermal-nanoparticles followed by NIR-irradiation did not significantly kill biofilm-inhabitants. This indicates that the biofilm mode of growth poses a barrier to penetration of photothermal-nanoparticles, yielding dissipation of heat to the biofilm-surrounding rather than in its interior. Staphylococcal biofilm-growth in the presence of photothermal-nanoparticles could be significantly prevented after NIR-irradiation because PDA-NPs were incorporated in the biofilm and heat dissipated inside it. Thus, unmodified photothermal nanoparticles have potential for prophylactic infection-control, but data also constitute a warning for possible development of thermo-resistance in infectious pathogens.

The Effect of the Molecular Weight of Polyvinylpyrrolidone and the Model Drug on Laser-Induced In Situ Amorphization.

Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (Tg) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (Mw) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different Mw of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer Mw on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes-Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest Mw (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.

Glycan targeting nanoparticle for photodynamic immunotherapy of melanoma.

Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP. Sambucus nigra agglutinin (SNA), a sialic acid-binding lectin, was employed to block CD24 and to enhance phagocytosis in melanoma tumours. In addition, we prepared SNA-conjugated hollow gold-iron oxide nanoparticles for photothermal therapy of tumours. Our findings show that the combination treatment of SNA-conjugated photothermal nanoparticles and near-infrared exposure successfully augments tumour cell phagocytosis both in vitro and in vivo models.

Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo.

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(ß-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm.

Hybrid donor-acceptor polymer nanoparticles and combination antibiotic for mitigation of pathogenic bacteria and biofilms.

Biofilms pose a significant clinical problem in skin and soft tissue infections. Their resistance to antibiotics has spurred investigations into alternative treatments, such as nanoparticle-mediated photothermal ablation. Non-toxic Hybrid Donor- Acceptor (DA) Polymer nanoParticles (H-DAPPs) were developed for fluorescence imaging (using poly(3-hexylthiophene-2,5 diyl) (P3HT)) and rapid, near-infrared photothermal ablation (NIR- PTA) (using poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe)). H-DAPPs were evaluated alone, and in combination with antibiotics, against planktonic S. aureus and S. pyogenes, and S. aureus biofilms. H-DAPPs NIR-PTA (15-700 µg/ mL) can generate rapid temperature changes of 27.6-73.1 °C, which can eradicate planktonic bacterial populations and reduce biofilm bacterial viability by more than 4- log (> 99.99%) with exposure to 60 s of 800 nm light. Reductions were confirmed via confocal analysis, which suggested that H-DAPPs PTA caused bacterial inactivation within the biofilms, but did not significantly reduce biofilm polysaccharides. SEM imaging revealed structural changes in biofilms after H-DAPPs PTA. S. aureus biofilms challenged with 100 µg/mL of H-DAPPs (H-DAPPs-100) to induce an average temperature of 55.1 °C, and the minimum biofilm eradication concentration (MBEC) of clindamycin, resulted in up to ~3- log decrease in bacterial viability compared to untreated biofilms and those administered H-DAPPs-100 PTA only, and up to ~2- log compared to biofilms administered only clindamycin. This study demonstrates that polymer nanoparticle PTA can mitigate biofilm infection and may improve antimicrobial efficacy.

Carbon dot-polymer nanoporous membrane for recyclable sunlight-sterilized facemasks.

Facemasks are considered the most effective means for preventing infection and spread of viral particles. In particular, the coronavirus (COVID-19) pandemic underscores the urgent need for developing recyclable facemasks due to the considerable environmental damage and health risks imposed by disposable masks and respirators. We demonstrate synthesis of nanoporous membranes comprising carbon dots (C-dots) and poly(vinylidene fluoride) (PVDF), and demonstrate their potential use for recyclable, self-sterilized facemasks. Notably, the composite C-dot-PVDF films exhibit hydrophobic surface which prevents moisture accumulation and a compact nanopore network which allows both breathability as well as effective filtration of particles above 100 nm in diameter. Particularly important, self-sterilization occurs upon short solar irradiation of the membrane, as the embedded C-dots efficiently absorb visible light, concurrently giving rise to elevated temperatures through heat dissipation.

A multifunctional dual-shell magnetic nanocomposite with near-infrared light response for synergistic chemo-thermal tumor therapy.

The synergistic tumor therapy in single nanoplatform has always been the goal for high efficacy tumor treatment while still remains great challenge. This paper reports a versatile nanotheranostic platform enlisting magnetic iron oxide nanoparticles, polydopamine (PDA), gold nanocages (Au nanocage) and metal organic framework (MOF, MIL101-NH2 ) in order to achieve synergistic chemothermal tumor therapy both in vitro and in vivo. The prepared magnetic photothermal nanoparticles (MPNPs) exhibit high drug loading capacity (31.34 mg/g), superior photo-thermal capacity (11.5°C enhancement in 180 s), low bio-toxicity, good magnetic resonance with a low dosage of 22 µg/g, as well as high antitumor efficacy in vivo. Such a novel and multifunctional nanoplatform is expected to find promising applications in target tumor synergistic therapy.

Dual targeting smart drug delivery system for multimodal synergistic combination cancer therapy with reduced cardiotoxicity.

This study first reports the development of a smart drug delivery system (DDS) for multimodal synergistic cancer therapy combining chemo-photothermal-starvation approaches. A magnetic photothermal agent was synthesized by preparing iron oxide (IO) nanoparticles (NPs) with covalently attached indocyanine green (ICG) and glucose oxidase (GOx) (ICGOx@IO). Synthesized ICGOx@IO NPs were co-encapsulated with doxorubicin (Dox) and EGCG ((-)-epigallocatechin-3-gallate) inside PLGA (poly(lactic-co-glycolic acid)) NPs using multiple emulsion solvent evaporation method. Such formulation gave the advantage of triggered drug release by near-infrared (NIR) laser irradiation (808 nm at 1 W/cm2). RGD peptide was attached to the surface of PLGA NPs and the final hydrodynamic size was around 210 nm. Dual targeting by peptide and 240 mT external magnet significantly improved cellular uptake. Cellular uptake was observed using FACS, electron and optical microscopy. Dual targeting along with laser irradiation could reduce in vitro cell viability by 90 ± 2% (Dox-equivalent dose: 10 µg/ml) and complete tumor ablation was achieved in vivo due to synergetic therapeutic effect. Another attractive feature of the DDS was the significant reduction of cardiotoxicity of doxorubicin by EGCG. This new platform is thus expected to hold strong promise for future multimodal combination therapy of cancers. STATEMENT OF SIGNIFICANCE: Doxorubicin is one of the most studied and effective chemotherapeutic agents whose application is hindered due to its cardiotoxicity. In this study, we used (-)-Epigallocatechin-3-gallate (EGCG) to overcome that limitation. However, drug delivery to tumor sites with no/minimum accumulation in healthy organs is always challenging. Although peptide-based targeting is very popular, the effectiveness of receptor/ligand binding active targeting is sometimes questioned which motivated us to apply dual targeting approach. Multimodal therapies can exhibit synergistic effects and subsequently reduce the required dose of drug over monotherapy. We aimed to achieve chemo-photothermal-starvation combination therapy in this study and such achievement is yet to be reported. Our developed system also has the advantage of triggered drug release by near-infrared (NIR) laser irradiation.

Inhibition of cancer cell migration with CuS@ mSiO2-PEG nanoparticles by repressing MMP-2/MMP-9 expression.

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

Remote Manipulation of a Microdroplet in Water by Near-Infrared Laser.

Facile manipulation of a tiny liquid droplet is an important but challenging issue for many miniaturized chemical and biological systems. Here we report that a microdroplet can be readily and remotely manipulated in aqueous environments under ambient conditions. The droplet is encapsulated with photothermal nanoparticles to form a liquid marble, and subsequently irradiated with a near-infrared (NIR) laser. The marble is able to ascend, shuttle, horizontally move, and even suspend in water by simply controlling the laser irradiation. Moreover, filling and draining of the marble can also be conducted on the water surface for the first time. This facile manipulation strategy does not use complicated nanostructures or sophisticated equipment, so it has potential applications for channel-free microfluidics, smart microreators, microengines, microrobots, and so on.

Near-infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging.

While thermo-chemotherapy has proved to be effective in optimizing the efficacies of cancer treatments, traditional chemotherapy is subject to adverse side effects and heat delivery is often challenging in operation. Some photothermal inorganic nanoparticles responsive to near infrared light provide new opportunities for simultaneous and targeted delivery of heat and chemotherapeutics to the tumor sites in pursuit of synergistic effects for efficacy enhancement. The state of the art of nanoparticle-induced thermo-chemotherapy is summarized and the advantages and challenges of the major nanoplatforms based on gold nanoparticles, carbon nanomaterials, palladium nanosheets, and copper-based nanocrystals are highlighted. In addition, the optical-imaging potentials of the nanoplatforms that may endow them with imaging-guided therapy and therapeutic-result-monitoring capabilities are also briefly discussed.