A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of Pseudomonas aeruginosa to the Native Quercetin

Quercetin (QUE)—a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in Pseudomonas aeruginosa—the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE–CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE’s bioactivities in the nanoplex. Compared to the native QUE, the QUE–CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of P. aeruginosa, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction.

Combined treatment of sorafenib and doxorubicin-loaded microbubble-albumin nanoparticle complex for hepatocellular carcinoma: A feasibility study

Purpose To assess the feasibility of the combined sorafenib (SOR) and doxorubicin-loaded microbubble-albumin nanoparticle complex (DOX-MAC) treatment effect in an orthotopic rat model of hepatocellular carcinoma (HCC). Materials and methods Sixty-two rats with N1-S1 hepatoma were divided into four groups according to the treatment methods, i.e. G1 (SOR and DOX-MAC; n = 12), G2 (SOR; n = 15), G3 (DOX-MAC; n = 12), G4 (DOX; n = 11), and G5 (normal saline; n = 12). We performed the theragnostic, contrast-enhanced ultrasound examination and treatment at the baseline, one-week, and two-weeks. Tumor volume and perfusion parameters were compared at each time point and the differences between all of the groups over time were analyzed using repeated measures ANOVA. We also analyzed the apoptotic index and microvessel density (MVD) per each tumor specimen in all of the groups. Results The tumors increased from the beginning in all of the groups to the final follow-up, whereas the tumor growth in the G1 group and the G2 group was inhibited during the treatment period compared to the baseline tumor volume (P = 0.016 and P = 0.031). The G1 group resulted in tumor growth inhibition compared to the control group (P = 0.008). The G1 group showed that the peak enhancement and wash-in area under the curve were lower than that of the G4 group (P = 0.010 and 0.022). However, there was no difference in perfusion parameters in the other treated group compared to control group. The MVD of the G1 group tumor was lower than that of the G4 group (P = .016). Conclusion Our results suggest that the combination therapy of SOR and DOX-MAC can cause inhibition of tumor growth after treatment and that this therapy can be adequately monitored using the theragnostic DOX-MAC agent.

Enhanced antitumor effects of follicle-stimulating hormone receptor-mediated hexokinase-2 depletion on ovarian cancer mediated by a shift in glucose metabolism

Background Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity. Results HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH β 33–53 or retro-inverso FSH β 33–53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway. Conclusions These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.

Enhanced Antitumor Effects of Follicle-stimulating Hormone Receptor-mediated Hexokinase-2 Depletion on Ovarian Cancer Mediated by a Shift in Glucose Metabolism

Background: Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity. Results: HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH β 33-53 or retro-inverso FSH β 33-53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway. Conclusions: These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.

THE ABSORPTION PROPERTIES OF GOLD NANO CONJUGATED WITH PROTEINS

The absorption properties of protein-conjugated metallic nanoparticles are theoretically investigated based on the Mie theory and the core-shell model. Our numerical calculations show that this finding is in good agreement with previous experiments. We provide a better interpretation of the origin of optical peaks in the absorption spectrum of the nanoparticle complex system. Our results can be used in biomedical applications.

Synthesis and antimicrobial activities of a metallic oxide nanoparticle complex of Moringa oleifera leaves extracts against selected microorganisms

This research work aimed at synthesizing and investigating the antimicrobial activities of a metallic oxide nanoparticle complex of Moringa oleifera leaves extracts against some microorganisms. Moringa oleifera leaves were washed, dried and blended. They were extracted with distilled water and ethanol using standard methods. The nanoparticle was synthesized by coordinating with manganese oxide. The physicochemical properties were determined following standard procedures. The phytochemical screening was carried out by standard methods. The antibacterial activities were done using agar well diffusion method. Antifungal activity was carried out following the plate technique. The leaves extract had a 75% yield and melting point of 116 °C while the nanoparticle had a yield of 60% and melted at 78 °C with pH of 3.46. The molar conductance of the nanoparticle revealed at 10.6 Ω−1cm2mol−1. The ethanolic extract of the leaves showed the presence of alkaloids, tannin, steroids and saponins. The ethanolic extract of M. oleifera exhibited the highest antibacterial activity of 33.05±0.10 mm against Bacillus subtilis while its antifungal activity revealed the highest inhibition of 48.40±0.53 mm at 30 mg/mL against Aspergillus niger. Staphylococcus aureus had a zone of inhibition of 19.00±0.16a using the aqueous extract. The ethanolic extract of M. oleifera nanoparticles showed antibacterial and antifungal activity against B. megaterium and A. niger with a zone of inhibition of 49.21±0.32 mm and 50.35±0.29 mm respectively while the aqueous extract showed antibacterial activity against S. aureus with a zone of 26.00±0.38mm. As it was concluded ethanolic extract in both leaves extract and its nanoparticle, possessed higher antibacterial and antifungal activities than the aqueous extract.