Action of chitosan-based solutions against a model four-species biofilm formed on cobalt-chromium and acrylic resin surfaces.

OBJECTIVE: To evaluate the anti-biofilm action of chitosan, nanoparticulate chitosan, and denture cleanser Nitradine™ against biofilms comprising Candida albicans, Candida glabrata, Staphylococcus aureus, and Streptococcus mutans. BACKGROUND: Biofilm removal from removable partial dentures (RPD) is important for success in prosthetic rehabilitation. MATERIALS AND METHODS: The anti-biofilm action of the experimental chitosan-based solutions and Nitradine™ was evaluated on acrylic resin and cobalt-chromium alloy through assessing cell viability, cell metabolism, residual aggregated biofilm, and extracellular polymeric substance and biofilm morphology. RESULTS: Only chitosan reduced the viability of C. albicans on cobalt-chromium alloy surface, by 98% (a 1.7 log10 reduction in cfu). Chitosan-based solutions neither promoted substantial alteration of the metabolic activity of the four-species biofilm nor reduced the amount of the aggregated biofilm. After immersion in chitosan and nanoparticulate chitosan, viable microorganisms and extracellular polymeric substances distributed over the entire specimens' surfaces were observed. Nitradine™ reduced the viability and metabolic activity of biofilm grown on both surfaces, but it did not remove all aggregated biofilm and extracellular polymeric substances. After immersion in Nitradine™, approximately 35% of the specimens' surfaces remained covered by aggregated biofilm, mainly composed of dead cells. CONCLUSION: Although chitosan and Nitradine™ promoted changes in the viability of microorganisms, neither solution completely removed the four-species biofilm from the Co-Cr and acrylic resin surfaces. Thus, isolated use of hygiene solutions is not indicated for biofilm control on RPDs; this requires complementary mechanical removal.

Determining growth inhibition of Candida albicans biofilm on denture materials after application of an organoselenium-containing dental sealant.

STATEMENT OF PROBLEM: Denture stomatitis is a chronic inflammatory condition caused by the formation of Candida albicans biofilm on denture bases. It is associated with aggravating intraoral pain, itching, and burning sensations. It can also potentiate cardiovascular diseases and aspiration pneumonia. The problem has thus far eluded efficient, toxic-free, and cost-effective solutions. PURPOSE: The purpose of this in vitro study was to investigate the effectiveness of organoselenium to inhibit the formation of C. albicans biofilm on the surface of acrylic resin denture base materials when it is either incorporated into the acrylic resin material or coated on the denture surface as a light-polymerized surface sealant. MATERIAL AND METHODS: Sixty heat-polymerized polymethyl methacrylate disks were fabricated and assigned to 4 groups (n=15): disks coated with a light-polymerized organoselenium-containing enamel surface sealant (DenteShield), disks impregnated with 0.5% organoselenium (0.5% selenium), disks impregnated with 1% organoselenium (1% selenium), and disks without organoselenium (control). C. albicans biofilm was grown on each disk which had been placed in a well of the microtiter plate containing 1-mL brain heart infusion broth inoculated with C. albicans. The plates were incubated aerobically at 37 °C for 48 hours. A confocal laser scanning microscope was used to determine the biofilm thickness, biomass, and live/dead cell ratio. Biofilm morphology was examined with scanning electron microscopy, whereas microbial viability was quantified by the spread plate method. The data were analyzed by using ANOVA and Tukey-Kramer multiple comparisons (α=.05). RESULTS: The microbial viability, biofilm thickness, biofilm biomass, and live/dead cell ratio were lower (P<.001) on disks in the test groups (DenteShield, 0.5% selenium, 1% selenium) when compared with the control group, with these variables being lowest in the 0.5% selenium and 1% selenium groups. The 0.5% selenium and 1% selenium groups did not differ significantly from each other in any of the variables (P>.05). Scanning electron microscope images showed inhibition of both biofilm growth and yeast to hyphae transition in the DenteShield, 0.5% selenium, and 1% selenium groups, with visible disruption of the biofilm morphology. CONCLUSIONS: The present study demonstrated that organoselenium, whether incorporated into or coated on the surface of an acrylic resin denture base material, has the potential to inhibit Candida albicans biofilm growth on denture surfaces and as such can be clinically useful for the prevention of denture stomatitis.

Anticandidal efficacy on polymide based denture resin using Photodynamic therapy, chemical and herbal disinfectants and their effect on surface roughness and hardness.

AIM: The present study aimed to evaluate the anticandidal effectiveness of PDT, DL, Triphala, CHX, and NE and their effects on Ra and the hardness of polyamide denture base colonized with C. Albicans. MATERIAL AND METHODS: A total of 50 thermo-injected polyamide denture resins were constructed and inoculated by the American Type Culture Collection (ATCC) of C. albicans in an in-vitro setup. The specimens were arbitrarily allocated into five groups, pre-candida count was measured then subjected to the diverse polyamide denture disinfection methodologies: Group 1: PDT, Group 2: Diode Laser, group 3: Triphala, group 4: 0.12% CHX (Control) and group 5 Neem extract. After disinfection protocol, post-candida count (CFU/ml) was assessed. Surface roughness and surface hardness of polyamide dentures were evaluated and statistical differences in the Ra and Vickers hardness was also assessed. Statistical analysis was performed for CFU/mL (log10) for exposed C. albicans by two-way ANOVA and Tukey's multiple test (p>0.05). For normality of the data, Kolmogorov Smirnov test was executed. RESULTS: The highest anti-microbial efficacy against Candida colonies was displayed by chemical control group 0.12% CHX (11.39 ± 1.8 CFU/ml). This was comparable to herbal NE (12.45 ± 2.9 CFU/ml) (p>0.05). There was no statistical difference found in the surface hardness values among the disinfected groups. Group 2: DL (1.32 ± 0.13 µm) showed the highest Ra value comparable to group 1: PDT (1.21 ± 0.22 µm) CONCLUSION: Polyamide denture base colonized with C. Albicans and disinfected with 0.12% Chlorhexidine and Neem extract demonstrated the highest antimicrobial efficacy with decreased surface roughness and no alteration in denture hardness.

Potential of antimicrobial topical gel with synthesized biogenic silver nanoparticle using Rhodomyrtus tomentosa leaf extract and silk sericin.

OBJECTIVE: Silver nanoparticles synthesized using Rhodomyrtus tomentosa leaf extract and silk sericin were used to functionalize carbopol 940 gel for topical applications. RESULTS: UV-vis spectra presented surface plasmon resonance at 426 nm, transmission electron microscopy revealed that nanoparticles were spherical with an average size of 25-50 nm. X-ray diffraction presented crystalline silver nanoparticles with zeta potential of ≈ - 30 mV. FTIR spectra showed a reduction of silver nitrate indicated by the shift in -OH at 2958 cm-1. The silver nanoparticle demonstrated broad-spectrum antimicrobial activity against Gram-positive, Gram-negative and fungi with MIC ranging between 0.26 and 2.10 µg mL-1, respectively. MIC of hydrogel ranged between 1.05-2.10 µg mL-1 with cell viability of 89%. Spreadability and extrudability of gel were 9.3 ± 0.85 s and 19.85 ± 0.03%, respectively with first order of fickian diffusion. CONCLUSIONS: The silver nanoparticle gel exhibited an effective antimicrobial property, hence can be exploited for topical applications.

Boron-based nanosheets for combined cancer photothermal and photodynamic therapy.

Tumor phototherapy is of great significance for the expansion and advancement of cancer treatment methods. Herein, two-dimensional boron nanosheets (B NSs) with a thickness of 2.4 nm exhibiting an excellent photothermal conversion performance were developed via a simple liquid phase ultrasonic stripping method. Following the loading of the photosensitizer agent chlorin e6 (Ce6) and subsequent modification with poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA), a B@Ce6-PAH-PAA NS nanomedicine exhibiting dual modal imaging-guided cancer photothermal therapy (PTT) and photodynamic therapy (PDT) properties, as well as outstanding stability was developed. The suitable nano-size (120 nm) of B@Ce6-PAH-PAA NSs can allow drugs to target tumor tissue with an enhanced permeability and retention effect (EPR). The cytotoxicity experiments demonstrated that B@Ce6-PAH-PAA NSs exhibited good biocompatibility even at high concentrations. Furthermore, the in vitro and in vivo experiments showed the excellent synergistic therapeutic effect of this nanomedicine for PTT and PDT.

Antioxidant, anti-inflammatory and healing potential of ethyl acetate fraction of Bauhinia ungulata L. (Fabaceae) on in vitro and in vivo wound model.

The present work aimed to investigate the antioxidant, anti-inflammatory and wound healing potential of ethyl acetate fraction from Bauhinia ungulata L. (FABU) on in vitro and in vivo models. Wound healing assay using human lung adenocarcinoma A549 cell line was employed to evaluate the ability of FABU in modulating cell migration. In addition, a surgical wound model in C57BL/6 mice was used to study the healing potential of FABU incorporated into gel carbomer 940 (Carbopol®). Evaluation of lipid peroxidation, inflammatory and anti-inflammatory mediator gene expression, rate of wound closure, and histological analysis were done. FABU significantly reduced the gap area in in vitro wound healing assay, 24 h after treatment. In the animal model, FABU at 0.5% topically applied once-daily for 5 days to the surgical wounds significantly reduced the lesion area. Moreover, it significantly decreased the levels of lipid peroxidation in the lesions and decreased the relative gene expression levels of IL-1ß and TNF-α in the injured region. In conclusion, our study suggests that Bauhinia ungulata can effectively promote the wound healing, probably by regulating the inflammatory environment during the early stages of the process.

Long-lasting anti-bacterial activity and bacteriostatic mechanism of tea tree oil adsorbed on the amino-functionalized mesoporous silica-coated by PAA.

Tea tree oil (TTO) is an efficient natural antibacterial agent. However, the bacteriostatic effect of TTO does not prevail for a long period because of the volatile nature of the oil. Therefore, a novel sustained-release formulation of TTO should be developed for improving the applicability of TTO. Herein, the mesoporous silica was selected for constructing a carrier for TTO. Mesoporous silica is non-toxic, easy to modify and exhibited an adjustable pore size. First, the mesoporous silica was modified by an aminated silane coupling agent (NH2-MCM-41). Then, the polyacrylic acid (PAA) was bonded by electrostatic bonds (PAA-NH2-MCM-41), which imparted the sustained-release effect in the TTO, supported in the mesoporous silica channel (TTO/PAA-NH2-MCM-41). The prepared bacteriostatic agent can achieve long-term sustained-release properties. At room temperature (26 ℃), the release rate of TTO after 11 h release reached 50 %. However, the release rate of TTO from TTO/PAA-NH2-MCM-8 reached only 42 % after 24 h. Furthermore, the sustained release behavior of TTO/PAA-NH2-MCM-41 was consistent with the Korsmeyer-Peppas kinetic model. Compared to TTO, TTO/PAA-NH2-MCM-41 exhibited a stable and sustained bacteriostatic effect even after 50 days in a natural environment. The minimum inhibitory concentration (MIC) value of the TTO/PAA-NH2-MCM-41 against Escherichia coli (E. coli) was 0.37∼0.44 mg/mL. TTO altered the cell morphology of E. coli and broke the integrity of the cell membrane, leading to cell death.

In situ surface modification on dental composite resin using 2-methacryloyloxyethyl phosphorylcholine polymer for controlling plaque formation.

Composite resins (CRs) are widely used as dental restorative materials for caries treatment. They cause problems of secondary caries since Streptococcus mutans stays in the dental plaque, which the surface exists and produces acidic compounds during metabolism. The dental plaque depositions are induced by the protein adsorption on the surface. Therefore, suppression of protein adsorption on the surface of the CRs is important for inhibiting the formation of plaque and secondary caries. In this study we developed a surface treatment to provide an antibiofouling nature to the CRs by chemical reaction with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers in the oral cavity during dental treatment. To carry out the photochemical reaction on the remaining polymerizable groups of CRs, we synthesized the MPC polymer with a polymerizable group in the side chain. The MPC polymer could bind on the surfaces of the CRs chemically under dental treatment procedures. The treated surface showed significant resistance to oral protein adsorption and bacterial adhesion even when the surface was brushed with a toothbrush. Thus, we concluded that the photochemical reaction of the MPC polymer with the CRs in the oral cavity was good for making an antibiofouling surface and preventing secondary caries.

Two-in-One Platform for High-Efficiency Intracellular Delivery and Cell Harvest: When a Photothermal Agent Meets a Thermoresponsive Polymer.

Efficient intracellular delivery of exogenous macromolecules is a key operation in biological research and for clinical applications. Moreover, under particular in vitro or ex vivo conditions, harvesting the engineered cells that maintain good viability is also important. However, none of the methods currently available is truly satisfactory in all respects. Herein, a "two-in-one" platform based on a polydopamine/poly( N-isopropylacrylamide) (PDA/PNIPAAm) hybrid film is developed, showing high efficiency in both cargo delivery and cell harvest without compromising cell viability. Due to the strong photothermal effect of PDA in response to near-infrared irradiation, this film can deliver diverse molecules to a number of cell types (including three hard-to-transfect cells) with an efficiency of ∼99% via membrane-disruption mechanism. Moreover, due to the thermoresponsive properties of PNIPAAm, the cells are harvested from the film without compromising viability by simply decreasing the temperature. A proof-of-concept experiment demonstrates that, using this platform, "recalcitrant" endothelial cells can be transfected by the functional ZNF580 gene and the harvested transfected cells can be recultured with high retention of viability and improved migration. In general, this "two-in-one" platform provides a reliable, universally applicable approach for both intracellular delivery and cell harvest in a highly efficient and nondestructive way, with great potential for use in a wide range of biomedical applications.

Preparation and characterization of chitosan/polyacrylic acid/copper nanocomposites and their impact on onion production.

Chitosan nanoparticles (CS-NPs) and chitosan/polyacrylic acid hydrogel nanoparticles (CS/PAA-HNPs) were obtained by ionic gelation with tripolyphosphate anions and copolymerization of CS with acrylic acid (AA), respectively. The prepared NPs were loaded by different concentrations of copper (1, 2 and 3% with respect to CS) to obtain chitosan/copper nanocomposites (CS/Cu-NCs) and chitosan/polyacrylic acid/copper hydrogel nanocomposites (CS/PAA/Cu-HNCs). The prepared NPs and their NCs were characterized by different techniques. The swelling properties and copper release from CS/Cu-NCs and CS/PAA/Cu-HNCs were evaluated. The antibacterial activity of the prepared samples against bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa), fungi, and yeast were investigated. The results displayed that the copper release, as well as the swelling percentage of CS/PAA/Cu-HNCs, were higher than that of CS/Cu-NCs. Furthermore, the impact of using CuSO4, CS/Cu-NCs, and CS/PAA/Cu-HNCs as a different source of copper on chlorophyll content, vegetative growth, minerals content, and the yield of onion plants during two seasons 2016 and 2017 were studied. It was found that the yield, plant growth, and nutrient content of onion bulbs were improved using CS/PAA-HNPs, which was loaded with 75 ppm copper, as foliar spray for onion plants.

Reduced Graphene-Oxide-Embedded Polymeric Nanofiber Mats: An "On-Demand" Photothermally Triggered Antibiotic Release Platform.

The steady increase of antimicrobial resistance of different pathogens requires the development of alternative treatment strategies next to the oral delivery of antibiotics. A photothermally activated platform based on reduced graphene oxide (rGO)-embedded polymeric nanofiber mats for on-demand release of antibiotics upon irradiation in the near-infrared is fabricated. Cross-linked hydrophilic nanofibers, obtained by electrospinning a mixture of poly(acrylic acid) (PAA) and rGO, show excellent stability in aqueous media. Importantly, these PAA@ rGO nanofiber mats exhibit controlled photothermal heating upon irradiation at 980 nm. Nanofiber mats are efficiently loaded with antibiotics through simple immersion into corresponding antibiotics solutions. Whereas passive diffusion based release at room temperature is extremely low, photothermal activation results in increased release within few minutes, with release rates tunable through power density of the applied irradiation. The large difference over passive and active release, as well as the controlled turn-on of release allow regulation of the dosage of the antibiotics, as evidenced by the inhibition of planktonic bacteria growth. Treatment of superficial skin infections with the antibiotic-loaded nanofiber mats shows efficient wound healing of the infected site. Facile fabrication and implementation of these photothermally active nanofiber mats makes this novel platform adaptable for on-demand delivery of various therapeutic agents.

Investigation of the factors affecting the photothermal therapy potential of small iron oxide nanoparticles over the 730-840 nm spectral region.

The use of superparamagnetic iron oxide nanoparticles (SPIONs) as a sensitizer in photothermal therapy (PTT) is relatively new and the origin of such a phenomenon is not known. Usually, large crystals and aggregated particles are preferred in the literature, suggesting that these increase the absorbance of particles at the irradiation wavelength, and hence, provide a larger temperature increase. This study has two major goals: identification of the key factors that affect the photo-induced temperature increase in well-controlled experiments and the influence of laser irradiation on nanoparticle properties. Small, biocompatible poly(acrylic acid) coated SPIONs (PAA/SPIONs) were used since they are more practical for future medical use than large aggregates. We studied the impact of three major laser-dependent variables, namely the wavelength (between 728 and 838 nm), intensity (1.85-9.76 W cm-2) and power (105-800 mW) as well as attenuation at the irradiation wavelength, on photothermal heating achieved with PAA/SPIONs. Within the studied range of these variables, only the laser power plays a critical role on the magnitude of photothermal heating in solutions. There is no strong correlation between the attenuation at the excitation wavelength and the temperature increase. In addition, extensive characterization of SPIONs before and after irradiation revealed no significant difference, which supports the re-usability of SPIONs. Lastly, the PTT potential of these small PAA/SPIONs was demonstrated in vitro on HeLa cells. At these low laser powers no temperature increase in SPION-free water or cell death in SPION-free cells was detected. Hence, this study provides a new insight into the photothermal effect of SPIONs, provides a clear and repeatable experimental procedure and demonstrates great potential for small SPIONs to be exploited in PTT.

Therapeutic Intervention of Aloe Gel Containing Nano-Sized and Micron-Sized Silver Sulfadiazine Gel on Second-Degree Burn: A Comparative Study.

The current work focuses on the formulation development, optimization, and in vivo assessment of nano-sized silver sulfadiazine ( nSSD) and micron-sized silver sulfadiazine ( mSSD) topical gel composed of Aloe vera gel ( Aloe gel) and Carbopol 940 for the management of second-degree burn wound. The optimized concentration of gel-forming agent (Carbopol 940) was chosen based on best possible consistency and spreadability of the gel. The second-degree burn infliction was developed in the posterior region of rats followed by anesthesia. Afterward, the created wounds were further treated individually by both the gel formulation (1 application daily) for 14 days and observations were recorded. The nSSD gel showed better wound healing and a higher degree of tissue hyperplasia as compared with mSSD gel in rats. In vitro drug release study showed better drug release from nSSD gel (74.25 ± 3.331%) as compared with mSSD gel formulation (61.32 ± 2.112%) after 24 hours. The nSSD and mSSD topical gel-treated rats showed 95.63% and 78.75% wound healing after 14 days, while in the case of control group rats, 48.65% wound contraction was seen after 14 days. Furthermore, the histopathological study revealed that the nSSD gel was more efficient in controlling the wound infection and showed better wound healing as compared with mSSD gel formulation.

Preparative Purification of Polyphenols from Aronia melanocarpa (Chokeberry) with Cellular Antioxidant and Antiproliferative Activity.

The aim of this study was the purification process of polyphenols from Aronia melanocarpa (chokeberry), and the purification parameters were optimised by adsorption and desorption tests. By comparing adsorption and desorption ability of polyphenols from chokeberry on six kinds of macroporous resin, XAD-7 resin was selected. Experiments prove that the best purification parameters of static adsorption and desorption were sample pH = 4.0 with 4 h of adsorption; and desorption solvent is 95% ethanol (pH = 7.0) with 2 h of desorption. The best dynamic parameters were 9.3 bed volume (BV) of sample loading amount at a feeding flow rate of 2 BV/h, and washing the column with 5.8 BV of water, followed by subsequent elution with an eluent volume of 5.0 mL at an elution flow rate of 2 BV/h. Next the antioxidant and antiproliferative activity of polyphenols from chokeberry, blueberries, haskap berries was studied on HepG2 human liver cancer cells. The results show that polyphenol from chokeberry has a strong antioxidant effect. Taking into account the content of polyphenols in fruit, polyphenols from chokeberry represent a very valuable natural antioxidant source with antiproliferative products.

Enhanced Hepatic Functions of Genetically Modified Mouse Hepatoma Cells by Spheroid Culture for Drug Toxicity Screening.

While hepatic cell lines are mainly used for in vitro drug induced toxicity studies, they exhibit limited functionalities. To overcome this, the authors have employed genetically engineered mouse hepatoma cells, Hepa/8F5, wherein expression of liver enriched transcription factors is induced by doxycycline leading to increased functionality. Further enhancement in functionality is achieved by spheroid culture in a previously developed 3D cell culture platform. Cells are seeded in presence of temperature-responsive poly(N-isopropylacrylamide) on poly(N-isopropylacrylamide--co-gelatin) cryogel scaffold based high throughput platform. Cells seeded in presence of poly(N-isopropylacrylamide) and induced with doxycycline exhibited highest functionalities. There is an increase of ≈26, 36, and 39% in albumin secretion, ammonia removal, and CYP3A4 activity, respectively. Morphological analysis showed arrest in cell proliferation and enlarged nucleus in presence of doxycyline and spheroid formation in presence of poly(N-isopropylacrylamide). Drug induced liver toxicity studies revealed that cells induced with doxycycline are resistive to tamoxifen but sensitive to acetaminophen whereas, cultures initiated in presence of poly(N-isopropylacrylamide) are resistive to both the drugs which is indicative of diffusional barrier of the spheroids. The authors conclude that Hepa/8F5 cells show enhanced functionality in cryogel based spheroid culture platform which can be successfully used for high throughput screening of hepatic toxicity in vitro.

Dietary psyllium fiber increases intestinal heat shock protein 25 expression in mice.

Heat shock proteins (HSPs) protect intestinal epithelial cell function, integrity and viability against many forms of stress. We hypothesized that dietary fibers (DFs) in the diet may increase HSP expression, since DFs are known to exhibit beneficial effects on intestinal health. The present study investigated the regulation of intestinal HSP expression by DFs, particularly psyllium fiber. Feeding psyllium fiber for 5 d increased HSP25 expression, but not HSP32 and HSP70 expression in the jejunum, ileum, and colon of mice at both the protein and mRNA levels. The increases in HSP25 expression did not correlate with cecal organic acid production by microbial fermentation. The water-insoluble fraction of psyllium fiber largely contributed to the induction of HSP25 expression, but feeding with other water-insoluble DFs from beet, wheat, and oats failed to induce intestinal HSP25 expression. Although the water-holding capacity of psyllium fiber was much higher than those of the other water-insoluble DFs examined, the increase in HSP25 expression induced by feeding polycarbophil, which possesses a high water-holding capacity similar to that of psyllium fiber, was much lower than that induced by psyllium fiber. Finally, induction of malondialdehyde production by hydrogen peroxide, an oxidant, in the colon of mice fed psyllium fiber was lower than that in mice fed with the control diets. Taken together, feeding psyllium fiber, especially the water-insoluble fraction, increases intestinal HSP25 expression and suppresses oxidant-induced malondialdehyde production.

Poly(acrylic acid) conjugated hollow mesoporous carbon as a dual-stimuli triggered drug delivery system for chemo-photothermal synergistic therapy.

In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment. The DOX loaded DOX/HMC-SS-PAA had a high drug loading amount up to 51.9%. The in vitro drug release results illustrated that DOX/HMC-SS-PAA showed redox and pH dual-responsive drug release, and the release rate could be further improved by the near infrared (NIR) irradiation. Cell viability experiment indicated that DOX/HMC-SS-PAA had a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This work suggested that HMC-SS-PAA exhibited dual-responsive drug release property and could be used as a NIR-adsorbing drug delivery system for chemo-photothermal synergistic therapy.

Tailored Synthesis of Octopus-type Janus Nanoparticles for Synergistic Actively-Targeted and Chemo-Photothermal Therapy.

A facile, reproducible, and scalable method was explored to construct uniform Au@poly(acrylic acid) (PAA) Janus nanoparticles (JNPs). The as-prepared JNPs were used as templates to preferentially grow a mesoporous silica (mSiO2 ) shell and Au branches separately modified with methoxy-poly(ethylene glycol)-thiol (PEG) to improve their stability, and lactobionic acid (LA) for tumor-specific targeting. The obtained octopus-type PEG-Au-PAA/mSiO2 -LA Janus NPs (PEG-OJNP-LA) possess pH and NIR dual-responsive release properties. Moreover, DOX-loaded PEG-OJNP-LA, upon 808 nm NIR light irradiation, exhibit obviously higher toxicity at the cellular and animal levels compared with chemotherapy or photothermal therapy alone, indicating the PEG-OJNP-LA could be utilized as a multifunctional nanoplatform for in vitro and in vivo actively-targeted and chemo-photothermal cancer therapy.

P-glycoprotein inhibitors: synthesis and in vitro evaluation of a preactivated thiomer.

The aim of this study was to synthesize the preactivated thiomer poly(acrylic acid)-cyteine-2-mercaptonicotinic acid (PAA-Cys-2MNA) and to evaluate its P-glycoprotein (P-gp) inhibitory properties. The thiomer (PAA-Cys) was synthesized by covalent immobilization of thiol groups on poly(acrylic acid) (PAA) with a molecular mass of 250 kDa followed by immobilization of 2-mercaptonicotinic acid (2MNA) to thiol groups via disulfide bond formation resulting in PAA-Cys-2MNA. P-gp inhibitory effect of this preactivated thiomer was evaluated on Caco-2 cells. Transports of rhodamine 123 at 37 °C with and without verapamil and at 4 °C were performed to evaluate P-gp function of cells. In total, 1571.81 ± 156.18 µmol thiol groups were immobilized per gram of polymer that were in the next step by 99.88% preactivated. The enhancement ratios of Papp calculated from the ratio between Papp of rhodamine 123 in the presence of P-gp inhibitors and Papp of rhodamine 123 alone were 2.36, 2.09, and 1.84-fold in the presence of PAA-Cys-2MNA, PAA-Cys, and PAA, respectively. Because of its pronounced P-gp inhibitory effect, PAA-Cys-2MNA could be considered as promising macromolecular P-gp inhibitor for various drug delivery systems.

Developmental and Reproductive Effects of Iron Oxide Nanoparticles in Arabidopsis thaliana.

Increasing use of iron oxide nanoparticles in medicine and environmental remediation has led to concerns regarding exposure of these nanoparticles to the public. However, limited studies are available to evaluate their effects on the environment, in particular on plants and food crops. Here, we investigated the effects of positive (PC) and negative (NC) charged iron oxide (Fe2O3) nanoparticles (IONPs) on the physiology and reproductive capacity of Arabidopsis thaliana at concentrations of 3 and 25 mg/L. The 3 mg/L treated plants did not show evident effects on seeding and root length. However, the 25 mg/L treatment resulted in reduced seedling (positive-20% and negative-3.6%) and root (positive-48% and negative-negligible) length. Interestingly, treatment with polyethylenimine (PEI; IONP-PC coating) also resulted in reduced root length (39%) but no change was observed with polyacrylic acid (PAA; IONP-NC coating) treatment alone. However, treatment with IONPs at 3 mg/L did lead to an almost 5% increase in aborted pollen, a 2%-6% reduction in pollen viability and up to an 11% reduction in seed yield depending on the number of treatments. Interestingly, the treated plants did not show any observable phenotypic changes in overall size or general plant structure, indicating that environmental nanoparticle contamination could go dangerously unnoticed.