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We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs., Competing Interests: The authors report no conflicts of interest in this work.

Breast cancer stem cells (BCSCs) are implicated in the initiation and progression of breast cancer and are responsible for metastasis and recurrence. In this study, we attempted to simultaneously target differentiated breast cancer cells (DBCCs) and BCSCs by using a combination of docetaxel (DTX)- and sulforaphane (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based nanoparticles. BCSCs were identified as having an ESA+CD44+CD24– phenotype, which exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited enhanced cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by down-regulating β-catenin expression. In vivo analysis of anti-tumor activity showed that the combination therapy with DTX- and SFN-loaded nanoparticles had the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN-loaded nanoparticle-treated groups. In conclusion, the combination of SFN- and DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment of breast cancer by simultaneously targeting DBCCs and BCSCs.

To develop biodegradable docetaxel-loaded self-assembled nanoparticles of poly (D,L-lactide-co-glycolide)/hyaluronic acid block copolymers were successfully synthesized. These copolymers could form nanoparticles with small size (<200 nm), an acceptable CMC (~7.9 mg/L), typical core/shell structure and superior stability in one week. DTX-loaded PLGA(502H)-b-HA(5.6k) nanoparticles (DTX/SANPs) showed a biphasic release pattern within 120 h, and exhibited enhanced cytotoxicity toward CD44-overexpressing MDA-MB-231 cells. Cellular uptake study indicated that PLGA(502H)-b-HA(5.6k) nanoparticles (SANPs) were taken up in MDA-MB-231 cells by CD44-mediated endocytosis. Pharmacokinetics study revealed DTX/SANPs could prolong the circulation of DTX in the blood. In vivo studies demonstrated that SANPs exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, DTX/SANPs have great potential for targeted chemotherapy for CD44-overexpressing breast cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin and are often resistant to chemotherapy and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. To achieve the goal of both targeting BCSCs and bulk breast cancer cells, we developed 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)-supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed that the size of all the nanoparticles was smaller than 200 nm. BCSCs were enriched from MCF-7 cells by a sphere formation method and identified with the CD44(+)/CD24(-) phenotype. Quantitative and qualitative analysis demonstrated that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres, revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7 mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7 xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity (reflecting by loss of body weight) in mice. Thus, this combination therapy may provide a potential strategy to improve the therapy of breast cancer by eradication of breast cancer cells together with BCSCs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The clinical use of immunotoxins is severely limited by nonspecific toxicity. To overcome this limitation, PE38KDEL was used as a model protein toxin to prepare PE38KDEL-loaded poly(lactic-co-glycolic acid) (PLGA) antibody modified nanoparticles (NPs), which were covalently conjugated with Fab' fragments of a humanized anti-HER2 monoclonal antibody (rhuMAbHER2) by a two-step carbodiimide method. The characterization of the PE38KDEL-loaded nanoparticles-anti-Fab' bioconjugates (PE-NPs-HER), such as particle size, zeta potential and morphology, were evaluated by dynamic light-scattering detector and transmission electron microscope (TEM). Micro BCA assay was used to determine the drug encapsulation efficiency and the quantity of Fab' conjugated with NPs. The binding affinity and internalization efficiency of PE-NPs-HER were demonstrated by flow cytometry and laser-scanning confocal microscopy. In comparison with PE38KDEL-loaded nanoparticles (PE-NPs) that lack anti-HER2 Fab', PE-NPs-HER had superior in vitro cytotoxicity against HER2-overexpressing breast cancer cell lines. Progressively, PE-NPs-HER has superior protective antitumor activity in HER2-overexpressing tumor-bearing mice than the control immunotoxin PE-HER constructed by chemically coupling PE38KDEL to rhuMAbHER2. Most strikingly, in developed HER2-overexpressing tumor xenograft model, administration of PE-NPs-HER (0.9 mg/kg) showed a much better therapeutic efficacy in inhibiting tumor growth compared with PE-HER and other controls: final mean tumor load was 13+/-6 mm(3) (mean+/-SD; n=8, significantly smaller than all other groups by ANOVA at 95% confidence interval). In addition, PE-NPs-HER were well tolerated in mice with a much higher MTD (maximally tolerated dose) than PE-HER (2.92 mg/kg vs. 0.92 mg/kg), indicating the systemic toxicity of PE38KDEL was dramatically reduced by PLGA encapsulation. Thus, the bioconjugates PE-NPs-HER may represent a potentially useful strategy for cancer therapy.

A new sulfur precursor with a highly reactive chemical nature was prepared with S powder and NaBH4 at the high temperature of 180 °C in a closed autoclave and made it possible to carry out the synthesis of high quality metal sulfide nanocrystals (NCs) with diverse composition and structure. Using this new sulfur source, we demonstrated aqueous synthesis of colloidal Cu-doped ZnCdS NCs (d-dots) with pure, color-tunable photoluminescence (PL) in a wide spectral range (from 517 to 650 nm) based on the ‘co-nucleation doping’ strategy. The influences of the various experimental variables, including Cd/Zn ratio, Cu-doping concentration, pH value and amount of mercaptopropionic acid (MPA), on the optical properties of Cu-doped ZnCdS NCs were systematically investigated. Furthermore, highly efficient and stable dopant emission from Cu:ZnCdS/ZnS core/shell d-dots with PL quantum yield as high as 40% was achieved by the deposition of a ZnS shell around the bare Cu:ZnCdS cores; this is the highest reported to date for aqueous doped NCs. The optical properties and structure of the d-dots were characterized by UV–vis absorption spectra, PL spectra, x-ray photoelectron spectroscopy, powder x-ray diffraction, and transmission electron microscopy. The experimental results indicated that this facile synthesis route would provide a versatile approach for the preparation of other water-soluble sulfide NCs. [ABSTRACT FROM AUTHOR]

Photodegradation of gas phase benzene by SnO2 nanoparticles has been studied in humid air, dry air and N2 by using a tubular photoreactor. The SnO2 nanoparticles are synthesized by the oxidation of anhydrous stannic chloride (SnCl4) in a propane/air turbulent flame. Direct hole oxidation and the ·OH radical mechanisms have been discussed based on experimental results. The goal of this research is to explore a viable and efficient alternative photocatalyst and photocatalytic process, in particular, for humidity-tolerant photocatalyst or photocatalytic process in environmental applications. [ABSTRACT FROM AUTHOR]