Bis(dipyridophenazine)(2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Hexafluorophosphate: A Lesson in Stubbornness

Ruthenium complexes are currently considered to be among the most promising alternatives to platinum anticancer drugs. In this work, thirteen structural analogues and organelle/receptor‐targeting peptide bioconjugates of a cytotoxic bis(dppz)‐Ru^II complex [Ru(dppz)₂(CppH)](PF₆)₂ ( 1 ) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine). It was observed that structural modifications (lipophilicity, charge, and size‐based) result in the cytotoxic potency of 1 being compromised. Confocal microscopy studies revealed that unlike 1 , the screened complexes/bioconjugates do not have a preferential accumulation in mitochondria. The results of this important structure–activity relationship strongly support our initial hypothesis that accumulation in mitochondria is crucial for 1 to exert its cytotoxic action.     

熔体静电纺聚乳酸纤维膜的制备、表征及细胞毒性评价

调试熔体静电纺聚乳酸(PLA)过程中的电压场和温度场的参数,对不同条件下的纤维膜进行测试,研究电压场与温度场与纤维直径间的关系,并评价熔体静电纺PLA膜的细胞毒性。以聚乳酸(PLA)为原料,采用熔体静电纺丝方法,电压调整在20~26 k V范围,空间温度在10~70℃之间,分别进行熔体纺丝实验,将制得的纤维膜进行细胞毒性评价。熔体静电纺丝PLA纤维的平均直径随电压的升高逐渐增大,当空间温度为50℃时,所得纤维平均直径为最小。细胞活力测试证实熔体静电纺PLA膜无细胞毒性,具有良好的组织工程材料的应用前景。     

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro,ex vivo and in vivo characterizations

Objective: The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan.

Methods: Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined.

Results: Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24?h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan.

Conclusion: These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.     

UV-enhanced toxicity of water-stable quantum dots in human pancreatic carcinoma cells

Zn-based (capped with thioglycolic acid (TGA) or 3-mercaptopropionic acid (MPA)) and Cd-based quantum dots (QDs) (capped with TGA or L-glutathione), were synthesised and used to investigate their cytotoxicity to human pancreatic carcinoma cells (PANC-1) in absence and presence of UV irradiation. Zn-based QDs exhibited less intrinsic cytotoxicity than the Cd-based QDs, however, the excitation of 50?µg/mL-QDs using UV lamp significantly enhanced the cytotoxicity of both QDs. After 15?min of UV irradiation, the viability for cells exposed to Cd-based QDs capped with TGA or glutathione was 49%?±?6% or 56%?±?3%, respectively. The corresponding cell viability in the control test was 83%?±?8% after 15?min of UV irradiation. In turn, the viability for cells exposed to Zn-based QDs capped with 3-MPA or TGA was 64%?±?3% and 52%?±?3%, respectively, after 30?min of UV irradiation; the cell viability in the control test was 80%?±?7% for the same UV irradiation time. Laser scanning confocal analyses evidenced that QDs can be easily ingested by PANC-1. Based on their good compositional stability, Zn-based QDs capped with 3-MPA can be considered a promising material for nanomedicine applications until concentrations of 200?µg/mL.     

细胞培养法评价铁铬钼软磁合金的生物相容性

为检测口腔中所用铁铬钼软磁合金的细胞毒性,以评价其生物相容性,将材料浸提液用于体外细胞培养,进行四唑盐(MTT)比色实验来评价材料的细胞毒性。结果表明,软磁合金的细胞毒性级为Ⅰ级,纯钛的毒性为0级。软磁合金组对细胞增殖的抑制作用大于纯钛组,但统计学分析结果显示,两种金属材料组与阴性对照组吸光度值之间的差异均无统计学意义(P>0.05)。软磁合金仅具有极微弱的细胞毒性,符合临床应用的要求,为其在义齿磁性固位体中的应用提供了生物学依据。     

Nanometric Micelles with Photo‐Triggered Cytotoxicity

The development of a photo‐responsive micellar system capable of triggering cell death is reported. Precursors of the micelles are synthesized by connecting a lipophilic chain to a hydrophilic polyethylene glycol via a photo‐labile nitrobenzyl group. The resulting amphiphilic units are self‐assembled in water forming 12 nm micelles that are readily internalized into cells. Upon photo‐irradiation, micelles undergo cleavage and yield a cytotoxic nitrosobenzaldehyde derivative, which significantly inhibits the proliferation of MDA‐MB‐231 cells under standard in vitro conditions.     

9H-xanthene-2,7-diols as antioxidants for autoxidation of linoleic acid

The antioxidant activities of 9H-xanthene-2,7-diols and α-tocopherol were studied during the oxidation of linoleic acid in a homogeneous solution and in an aqueous micelle dispersion. The antioxidant activities of 9H-xanthene-2,7-diols for both systems were 1.0–2.4 times greater relative to α-tocopherol. In addition, the 1,3,4,5,6,8-hexamethylxanthene-2,7-diol showed less cytotoxicity toward human fibroblasts than did 2,6-di-t-butyl-4-methylphenol.     

A cell suspension agar diffusion test using Neutral Red release to assess the relative irritancy potential of cosmetic ingredients and formulations

An established cytotoxicity test for plastic materials in medical devices has been adapted and used to assess the relative potential irritancy of cosmetic ingredients and formulations during product development. Serum-free medium containing a novel protein supplement supported growth in suspension of LS mouse fibroblast cells. Release of the vital dye Neutral Red from pre-loaded cells suspended in agar was the endpoint. Test substances and reference standards were applied to a central well cut into the agar, a sensitive method which allowed accurate dose application and yielded consistent results. Relative irritancy potential was measured quantitatively by comparing the diameters of the clear zones of damaged cells which surround the central well. The test has been used with raw materials such as surfactants, preservatives and herbal extracts, as well as finished products ranging from shampoos and conditioners to creams, lotions and coloured cosmetics. The method is practical, versatile, reproducible and economic to use.     

Variations in Cytotoxicity During Ozonation of Substituted Aromatics

The cytotoxicity test, using BGM cells and a colorimetric protein assay (Lowry, 1951) was a more sensitive modification of those described by Christian (1973) and Elias, et al. (1978). The cytotoxicity varied during ozonation, reaching a maximum after 50%90% degradation of the initial compound; aniline solution, 6.5x10³ M, showed a maximum cytotoxicity at 90% degradation after 60 min of ozonation, which decreased to 0% after 180 min 0₃. Ozonated nitro– and chloro–cresol solutions showed similar patterns. The variations in cytotoxicity seem to be related to the formation of intermediate oxidation products. The preliminary results suggest that this type of test, being both simple and fast, would be useful in toxicological screening of wastewater.     

河蚬汤纳米颗粒细胞毒性及对大鼠腹腔巨噬细胞吞噬功能的影响

许多传统食品中存在大量的伴生性纳米颗粒,其纳米尺度的构造赋予它们特殊的活性与功能,然而这类纳米颗粒对人体细胞的影响尚未被充分揭示。以河蚬汤及其伴生纳米颗粒为例,采用狗肾上皮细胞(MDCK)、人结肠腺癌细胞(Caco-2)、人正常肝细胞(L-02)和大鼠原代腹腔巨噬细胞模型,研究以液相色谱方法分离制备的河蚬汤纳米颗粒的细胞毒性,以及其对大鼠原代腹腔巨噬细胞功能的影响。实验结果表明:15.63~500.00μg/mL河蚬汤伴生纳米颗粒对4种细胞均无明显毒性;这些纳米颗粒能被大鼠原代腹腔巨噬细胞吞噬,对正常巨噬细胞的膜电位和吞噬功能无明显影响,抑制AAPH诱导氧化应激引起的细胞膜超极化,拮抗线粒体的氧化应激与细胞吞噬功能损伤。抗氧化测试结果显示,河蚬汤伴生纳米颗粒具有FRAP、ABTS抗氧化活力,但不具有ORAC活性。研究旨在为后续深入开展河蚬汤及其伴生纳米颗粒的功效以及作用机制提供必要的基础数据和理论支持。