生物功能化半导体量子点对活细胞内蛋白质分子可视化的研究进展

半导体量子点(或称半导体纳米微晶体)具有独特的光谱特性和良好的光化学稳定性。通过改变量子点的材料或粒径大小可在同一波长光激发下获得从紫外到近红外(或从蓝色到红色)波长范围内任意点的发射光谱。随着近年来生物亲和性功能化纳米技术的发展,为半导体量子点用于多通道、高通量对活细胞内蛋白质分子直接观察研究这一国际未解决的难题提供了可能。概述了生物功能化半导体量子点在活细胞生理条件对蛋白质分子进行可视化研究的最新进展,评价了其作为荧光探针对活细胞蛋白质分子进行实时动态研究的发展前景。     

Enhancement of cellular uptake,transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation

Aim:

Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV.

Methods:

SQV nanocrystals were prepared using anti-solvent precipitation–high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC.

Results:

The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (C_max) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.

Conclusion:

The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.     

Nanocomposites Based on Luminescent Colloidal Nanocrystals and Polymeric Ionic Liquids towards Optoelectronic Applications

Polymeric ionic liquids (PILs) are an interesting class of polyelectrolytes, merging peculiar physical-chemical features of ionic liquids with the flexibility, mechanical stability and processability typical of polymers. The combination of PILs with colloidal semiconducting nanocrystals leads to novel nanocomposite materials with high potential for batteries and solar cells. We report the synthesis and properties of a hybrid nanocomposite made of colloidal luminescent CdSe nanocrystals incorporated in a novel ex situ synthesized imidazolium-based PIL, namely, either a poly(N-vinyl-3-butylimidazolium hexafluorophosphate) or a homologous PIL functionalized with a thiol end-group exhibiting a chemical affinity with the nanocrystal surface. A capping exchange procedure has been implemented for replacing the pristine organic capping molecules of the colloidal CdSe nanocrystals with inorganic chalcogenide ions, aiming to disperse the nano-objects in the PILs, by using a common polar solvent. The as-prepared nanocomposites have been studied by TEM investigation, UV-Vis, steady-state and time resolved photoluminescence spectroscopy for elucidating the effects of the PIL functionalization on the morphological and optical properties of the nanocomposites.     

Achievement of safer palladium nanocrystals by enlargement of {100} crystallographic facets

Developing catalytic and safe nanomaterials is very necessary for the reduction of potential risk to human health; however, this strategy has been found extremely challenging because the enhancement in catalytic activity of nanomaterials is inevitably accompanied with more potent cell injury. The relationship of physicochemical properties and biological responses in catalytic nanomaterials needs to be clarified at the nano–bio interface for achieving the safe application. Herein, high-energy crystallographic facets of palladium (Pd) nanocrystals that have been known to significantly contribute to the catalytic activity were introduced to attenuate the toxicity, and the underlying mechanism was unraveled. Polyhedral Pd nanocrystals with morphology evolution from truncated octahedron to cuboctahedron and cube were prepared for elaborately tuning the extents of high-energy {100} facets, and hierarchical in vitro and in vivo biological evaluation were performed to clarify that Pd nanocrystals exposed with the more {100} facets could show the less toxicity to cells and animals. Density functional theory (DFT) calculation revealed {100} facet exposure was endowed with a strong oxygen adsorption, which weakens the breakage of the water molecule and suppresses the hazardous water dissociation and hydroxyl radical generation, which was supported by electron spin resonance (ESR)–based radical evaluation and X-ray photoelectron spectroscopy (XPS)-based oxygen identification. This means high-energy facet-based catalytic Pd nanocrystals can deliver low toxicity due to their unique surface properties.     

Hydrophobic sodium fluoride‐based nanocrystals doped with lanthanide ions: assessment of in vitro toxicity to human blood lymphocytes and phagocytes

In vitro immunotoxicity of hydrophobic sodium fluoride‐based nanocrystals (NCs) doped with lanthanide ions was examined in this study. Although there is already a significant amount of optical and structural data on NaYF₄ NCs, data on safety assessment are missing. Therefore, peripheral whole blood from human volunteers was used to evaluate the effect of 25 and 30 nm hydrophobic NaYF₄ NCs dissolved in cyclohexane (CH) on lymphocytes, and of 10 nm NaYF₄ NCs on phagocytes. In the concentration range 0.12–75 µg cm^?2 (0.17–106 µg ml^?1), both 25 and 30nm NaYF₄ NCs did not induce cytotoxicity when measured as incorporation of [³H]‐thymidine into DNA. Assessment of lymphocyte function showed significant suppression of the proliferative activity of T‐lymphocytes and T‐dependent B‐cell response in peripheral blood cultures (n = 7) stimulated in vitro with mitogens phytohemagglutinin (PHA) and pokeweed (PWM) (PHA > PWM). No clear dose–response effect was observed. Phagocytic activity and respiratory burst of leukocytes (n = 5–8) were generally less affected. A dose‐dependent suppression of phagocytic activity of granulocytes in cultures treated with 25 nm NCs was observed (vs. medium control). A decrease in phagocytic activity of monocytes was found in cells exposed to higher doses of 10 and 30 nm NCs. The respiratory burst of phagocytes was significantly decreased by exposure to the middle dose of 30 nm NCs only. In conclusion, our results demonstrate immunotoxic effects of hydrophobic NaYF₄ NCs doped with lanthanide ions to lymphocytes and to lesser extent to phagocytes. Further research needs to be done, particularly faze transfer of hydrophobic NCs to hydrophilic ones, to eliminate the solvent effect. Copyright © 2014 John Wiley & Sons, Ltd.     

The Use of Cellulose Nanocrystals for Potential Application in Topical Delivery of Hydroquinone

Nanotechnology‐based drug delivery systems can enhance drug permeation through the skin and improve the drug stability. The biodegradability and biocompatibility of cellulose nanocrystals have made these nanoparticles good candidates to use in biomedical applications. The hyperpigmentation is a common skin disorder that could be caused by number of reasons such as sun exposure and pregnancy. Hydroquinone could inhibit the production of melanin and eliminate the discolorations of skin. This study is aimed at introducing cellulose nanocrystals as suitable carriers for drug delivery to skin. Prepared cellulose nanocrystals were characterized by dynamic light scattering and atomic force microscopy. The size of cellulose nanocrystals determined using dynamic light scattering was 301 ± 10 nm. Hydroquinone–cellulose nanocrystal complex was prepared by incubating of hydroquinone solution in cellulose nanocrystals suspension. The size of hydroquinone–cellulose nanocrystal complex determined using dynamic light scattering was 310 ± 10 nm. The hydroquinone content of the hydroquinone–cellulose complex was determined using UV/vis spectroscopy. Hydroquinone was bound to cellulose nanocrystals representing 79.3 ± 2% maximum binding efficiency when 1.1 mg hydroquinone was added to 1 mL of cellulose nanocrystals suspension (2 mg cellulose nanocrystal). The hydroquinone–cellulose nanocrystal complex showed an approximately sustained release profile of hydroquinone. Approximately, 80% of bound hydroquinone released in 4 h.     

纳米晶体药物研究进展

纳米晶体技术能够有效提高难溶性药物的溶解度和溶出速度,从而提高其口服生物利用度,降低食物效应,是难溶性药物递送系统最具潜力的研究方向。在调研国内外文献的基础上,本文就纳米晶体药物的特点、组成、制备技术、临床应用及纳米效应的定量表达等方面的研究进展进行综述。     

纳米晶体药物研究进展

纳米晶体技术能够有效提高难溶性药物的溶解度和溶出速度,从而提高其口服生物利用度,降低食物效应,是难溶性药物递送系统最具潜力的研究方向。在调研国内外文献的基础上,本文就纳米晶体药物的特点、组成、制备技术、临床应用及纳米效应的定量表达等方面的研究进展进行综述。     

姜黄素纳米混悬液的制备及体内药动学

目的 优化处方工艺,制备稳定的姜黄素纳米晶混悬液,以提高溶出和生物利用度.方法 通过Box-Behnken设计优化姜黄素纳米晶混悬液的处方工艺,并监测粒度和电位的稳定性,通过差示扫描量热分析(DSC)和X射线粉末衍射分析(XRPD)考察研磨前后晶型变化,并通过体外溶出和大鼠体内药动学评价该制剂的体内外释放特征.结果 最...