Targeted Therapy with Cisplatin-Loaded Calcium Citrate Nanoparticles Conjugated with Epidermal Growth Factor for Lung Cancer Treatment.

Lung cancer is the leading cause of cancer-related deaths worldwide with high incidence rates for new cases. Conventional cisplatin (CDDP) therapy has limitations due to severe side effects from nonspecific targeting. To address this challenge, nanomedicine offers targeted therapies. In this study, cisplatin-loaded calcium citrate nanoparticles conjugated with epidermal growth factor (CaCit@CDDP-EGF NPs) were synthesized. The resulting nanodrug had a size below 350 nm with a cation charge. Based on density functional theory (DFT), the CaCit@CDDP NP model containing two citrates substituted on two chlorides exhibited a favorable binding energy of -5.42 eV, and the calculated spectrum at 261 nm closely matched the experimental data. CaCit@CDDP-EGF NPs showed higher inhibition rates against EGFR-expressed and mutant carcinoma cells compared to those of cisplatin while displaying lower cytotoxicity to lung fibroblast cells. Integrating in vitro experiments with in silico studies, these nanoparticles hold promise as a novel nanomedicine for targeted therapy in clinical applications.

Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiellapneumoniae infections.

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mortality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations provide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.

"Assessing exposure of printing factory workers in thailand to selected heavy metals using urine and hair as non-invasive matrices".

BACKGROUND: There are few thorough studies on the extent and inter-element relationships of heavy metal contamination in printing factory workers, especially in developing countries. The objective of this study was to determine the levels of eight heavy metals, including arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), cobalt (Co), lead (Pb), mercury (Hg), and manganese (Mn), in urine and scalp hair of printing industry workers, and assess inter-element correlations. METHODS: We examined a total of 85 urine samples and 85 scalp hair samples (3 cm hair segments taken from near the scalp) in 85 printing workers from a printing house in Bangkok, Thailand. We used an interviewer-administered questionnaire about participants' printing techniques, work characteristics, and work environment. Urine and scalp hair samples were analyzed for levels of each element using the inductively coupled plasma optical emission spectrometry (ICP-OES) technique. RESULTS: As, Cd, Cr, Ni, Pb were detected in urine with the geometric mean concentration range of 0.0028-0.0209 mg/L, and Hg, Pb, Ni, Cd, Co, Mn, Cr were detected in hair samples (0.4453-7.165 mg/kg dry weight) of printing workers. The geometric mean Ni level was significantly higher in the urine of production line workers than back-office personnel (0.0218 mg/L vs. 0.0132 mg/L; p = 0.0124). The other elements did not differ significantly between production line and back-office workers in either urine or hair. There was also a strong, statistically significant positive correlation between Ni and Co levels in hair samples of workers (r = 0.944, p < 0.0001). CONCLUSIONS: Average concentrations of most of the metals in urine and hair of printing workers were found to be above the upper reference values. The significantly higher concentrations of Ni in production line workers might be due to more exposure to printed materials. A strong inter-element correlation between Ni and Co in hair samples can increase stronger health effects and should be further investigated. This study reveals possible dependencies and impact interactions of heavy metal exposure in printing factory workers.

Development of Eugenol-Embedded Calcium Citrate Nanoparticles as a Local Anesthetic Agent.

Eugenol is a major phenolic component derived from clove oil with potential medical applications. Of particular interest, it has been used as a therapeutic agent in topical applications because of its analgesic and local anesthetic properties. However, topical formulations of eugenol produce skin irritation, which limits its clinical applications. One promising strategy to overcome this disadvantage is by using a biocompatible material that could be an appropriate topical vehicle for eugenol. Researchers have recently focused on the development of eugenol-embedded calcium citrate nanoparticles (Eu-CaCit NPs) without adverse effects. The Eu-CaCit NPs were developed as a topical delivery system and their biocompatibility and penetration ability were evaluated. Eu-CaCit NPs at 1.2 mg/mL did not show cytotoxicity effects in human cells. Moreover, the Eu-CaCit NPs presented the ability to penetrate the dermis layer of the human intact skin following 12 h exposure. All the results concluded that Eu-CaCit NPs have shown a potential as a carrier for topical delivery of eugenol. These novel nanoparticles represent a promising alternative for topical application of local anesthetic with natural pain relievers.

Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections.

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

Biguanide-Based Synthesis of 1,3,5-Triazine Derivatives with Anticancer Activity and 1,3,5-Triazine Incorporated Calcium Citrate Nanoparticles.

Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines-HCT116 and SW620. 2c and 3c which are the derivatives containing o-hydroxyphenyl substituents exhibited the highest activity with IC50 against both cell lines in the range of 20-27 µM, which is comparable to the IC50 of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative 2a. Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, "CaCit-2a NPs" were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of 2a from the synthesised CaCit-2a NPs is pH-responsive, and 2a could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.

Effect of Gold Nanoparticles on the TLR2-Mediated Inflammatory Responses Induced by Leptospira in TLR2-Overexpressed HEK293 Cells.

Leptospira infection can cause potential hazards to human health by stimulating inflammation, which is mediated mainly through the Toll-like receptor 2 (TLR2) pathway. Gold nanoparticles (AuNPs) are promising for medical applications, as they display both bioinert and noncytotoxic characteristics. AuNPs have been shown to have the ability to modify immune responses. To understand the in vitro immunomodulatory effect of AuNPs in a Leptospira infection model, the activation of TLR2 expression was examined in HEK-Blue-hTLR2 cells treated with Leptospira serovars and/or AuNPs (10 and 20 nm). The ability of AuNPs to modulate an inflammatory response induced by Leptospira was examined in terms of transcript expression level modulation of three proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß and IL-6) using two-stage quantitative real-time reverse transcriptase PCR. The results revealed that the administration of 10 nm AuNPs could augment the Leptospira-induced TLR2 signaling response and upregulate the expression of all three cytokine gene transcripts, whereas the 20 nm AuNPs attenuated the TLR2 activation and expression of proinflammatory cytokines. This indicates that AuNPs can modulate inflammatory parameters in Leptospira infection and different-sized AuNPs had different immunomodulatory functions in this model.

Feeding Cells with a Novel "Trojan" Carrier: Citrate Nanoparticles.

In this work, the preparation of novel calcium citrate (CaCit) nanoparticles (NPs) has been disclosed and the use of these NPs as "Trojan" carriers has been demonstrated. The concentration ratio between calcium ions and citrate ions was optimized, yielding spherical NPs with size in the range of 100-200 nm. Additionally, a fluorescent dye, fluorescein isothiocyanate (FITC), was successfully encapsulated by the coprecipitation method. The products were characterized by thermogravimetric analysis and scanning electron microscopy. The cellular uptake was investigated by incubating the synthesized fluorescent-tagged NPs with human keratinocytes using a confocal microscope. The accumulation of the FITC in the cells suggested that the CaCit NPs can potentially be used as novel drug carriers.

Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer.

One of the challenges in using a bone-spacer to cure infection is the fabrication of a material that can continuously release required antibiotics at effective concentrations for at least 4-6 weeks. Poly(methyl methacrylate) (PMMA) impregnated with antibiotics is one of the popularly used bone-spacer materials. Currently, improved sustained release of hydrophobic and hydrophilic antibiotics is needed for this material. Here, hydrophilic vancomycin (VAN) was encapsulated into calcium citrate (CC) particles and natural rice granules, and hydrophobic erythromycin (ERY) was encapsulated into ethyl cellulose and poly(lactic-co-glycolic acid) particles. The four antibiotic-loaded particles were each incorporated into the PMMA cement. The two unencapsulated drugs and all four drug-loaded particles distributed well in the obtained composites. PMMA composited with VAN-loaded CC showed prolonged VAN release at an effective concentration for more than 40 days, but the composite possessed lesser compressive strength than the PMMA with no drug. PMMA composited with unencapsulated ERY showed a better sustainment of drug release than those composited with encapsulated ERY. VAN elution from the VAN-CC-PMMA did not significantly affect the compressive strength of the material, whereas ERY elution from the ERY-PMMA composite significantly decreased the material's mechanical strength.

N-acetylcysteine reverses the decrease of DNA methylation status caused by engineered gold, silicon, and chitosan nanoparticles.

Introduction: Engineered nanoparticles (ENPs) are one of the most widely used types of nanomaterials. Recently, ENPs have been shown to cause cellular damage by inducing ROS (reactive oxygen species) both directly and indirectly, leading to the changes in DNA methylation levels, which is an important epigenetic mechanism. In this study, we investigated the effect of ENP-induced ROS on DNA methylation. Materials and methods: Human embryonic kidney and human keratinocyte (HaCaT) cells were exposed to three different types of ENPs: gold nanoparticles, silicon nanoparticles (SiNPs), and chitosan nanoparticles (CSNPs). We then evaluated the cytotoxicity of the ENPs by measuring cell viability, morphology, cell apoptosis, cell proliferation, cell cycle distribution and ROS levels. Global DNA methylation levels was measured using 5-methylcytosine immunocytochemical staining and HPLC analysis. DNA methylation levels of the transposable elements, long interspersed element-1 (LINE-1) and Alu, were also measured using combined bisulfite restriction analysis technique. DNA methylation levels of the TEs LINE-1 and Alu were also measured using combined bisulfite restriction analysis technique. Results: We found that HaCaT cells that were exposed to SiNPs exhibited increased ROS levels, whereas HaCaT cells that were exposed to SiNPs and CSNPs experienced global and Alu hypomethylation, with no change in LINE-1 being observed in either cell line. The demethylation of Alu in HaCaT cells following exposure to SiNPs and CSNPs was prevented when the cells were pretreated with an antioxidant. Conclusion: The global DNA methylation that is observed in cells exposed to ENPs is associated with methylation of the Alu elements. However, the change in DNA methylation levels following ENP exposure is specific to particular ENP and cell types and independent of ROS, being induced indirectly through disruption of the oxidative defense process.

Molecular and Morphological Evidence of Hepatotoxicity after Silver Nanoparticle Exposure: A Systematic Review, In Silico, and Ultrastructure Investigation.

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

Effect of gold nanoparticles on spermatozoa: the first world report.

OBJECTIVE: To evaluate the spermatotoxicity of gold nanoparticles. DESIGN: Experimental study. SETTING: A university in Thailand. PATIENT(S): Single-donor fresh semen sample. INTERVENTION(S): A mixture of gold nanoparticle solution and semen was prepared and further analyzed. MAIN OUTCOME MEASURE(S): Spermatozoa appearance. RESULT(S): After mixing the semen with a gold nanoparticle solution, 25% of sperm were not motile. Penetration of gold nanoparticle into the sperm heads and tails was observed. CONCLUSION(S): Spermatotoxicity of the gold nanoparticle can be detected.

Identification of gold nanoparticle in lymphocytes: a confirmation of direct intracellular penetration effect.

OBJECTIVE: Nanoparticles differ from the same material at larger scale in chemical and physical properties. The effect of nanoparticle on the blood cell still needs scientific verification. METHODS: The direct effect of gold nanoparticles on lymphocyte was direct assessed by in vitro assay. RESULTS: In this work, the author reported additional results from specific observation on lymphocyte exposure to gold nanoparticle. CONCLUSION: This result confirms for direct intracellular penetration effect.

Gold nanoparticle as an alternative tool for a urine pregnancy test.

OBJECTIVE: The urine pregnancy test is an easily available diagnostic test in the present day and is routinely performed. The test is based on an immunochromatography technique. Here, we used an advanced nanomedicine technique for modification of the urine pregnancy test. MATERIALS AND METHODS: The preparation of gold nanoparticle solution in this study followed the standard method. We performed an experiment on both pregnancy-positive and -negative urine samples. First, a mixture with an equal amount (500 microliters) of gold nanoparticle solution and urine sample was prepared. Then, it was further tested for pregnancy by the urine pregnancy test strip. RESULTS: The pregnancy-positive mixture became pink, while the pregnancy-negative mixture became gray. The urine pregnancy test strip for a positive mixture had two lines, while the negative mixture had one line. CONCLUSION: This application can help the diagnosis of pregnancy and can be an alternative method for a urine pregnancy test. To our knowledge, this is the first report on this application.

Effect of gold nanoparticle on renal cell: an implication for exposure risk.

OBJECTIVE: The objective of this study was to evaluate the effect of gold nanoparticles on renal cell. INTERVENTION: This study was performed as an experimental study. A mixture of gold nanoparticle solution and renal cell sediment was prepared and further analyzed. RESULTS: This work revealed that after mixing the renal cell sediment with gold nanoparticle solution, gold nanoparticles can be seen within the renal cells. CONCLUSIONS: Conclusively, the gold nanoparticle can penetrate into renal cell. This is the first report on this observation, and further implies the possibility of other nanoparticle nephrotoxicity in the present nanomaterial era.

Electronic absorption spectroscopy probed side-chain movement in chromic transitions of polydiacetylene vesicles.

Thermochromism, solvatochromism, and alkalinochromism of a poly-10,12-pentacosadiynoic acid (poly(PCDA)) vesicle solution are studied by electronic absorption spectroscopy. The spectroscopic profiles reveal different sequences of side-chain movement during the chromic transitions. The gradual hypsochromic shift and reversibility of the purple solution at low temperature in the thermochromic transition indicates that the transition starts with reversible conformational alteration of methylene side chains leading to metastable purple vesicles. Further heating to 80 degrees C or higher eventually causes the hydrogen bonds at the carboxylic head groups to break and turns the vesicle solution to red. The irreversibility of the red vesicles indicates that it is the most thermodynamically stable form. In the ethanolochromism and alkalinochromism, the processes are however induced at the vesicle-media interface, directly bringing about the hydrogen bond breaking. The purple solutions observed in the ethanolochromism and alkalinochromism cannot reverse back to the blue one. The absorption spectra clearly demonstrate that they are mixtures of the blue and red vesicles.

Gold nanoparticle as an alternative tool for urine microalbumin test: the first world report.

UNLABELLED: Urine microalbuminuria is a common indicator for occult preclinical nephropathy. At present, urine microalbumin test is routinely performed by clinical chemistry test. Here, the authors used the advanced nanomedicine technique for modification of the urine microalbumin test. MATERIALS AND METHODS: The preparation of gold nanoparticle solution in this study was according to the standard method reported by Frenkel et al. The author performed an experiment on both microalbumin positive and negative urine samples. First, the mixture between equal amount (500 microliter) of gold nanoparticle solution and urine sample was prepared. RESULTS: The microalbumin-positive mixture becomes purple, while the pregnancy-negative mixture becomes gray. CONCLUSION: This application can help the diagnosis of microalbumin and can be the alternative way for this urine microalbumin test. This is the first world report on this application.

Stilbene-bridged tert-butylcalix[4]arene as photoswitchable molecular receptors.

Using a designed control of conformations of tert-butylcalix[4]arene between cone and pinched cone, a highly selective receptor for small electron-deficient molecules with photoswitching binding ability was attained. [reaction: see text]