查找使用阿拉丁产品的科研文献

An acid-seeking carrier-free drug achieves high antitumor activity via a “solution-particle” transition

Xiaoying Zhang,Cuifeng Wang,Jiamin Wu,Yajun Liu,Zeping Yang,Ye Zhang,Xiaofeng Sui,Min Li,Min Feng

Drug nanocarriers that have long been expected to revolutionize cancer therapy have yet to achieve the significant clinical success. Therefore, it remains controversial to pursue a complex drug nanocarrier that lacks clinical relevance. Herein, we developed an easily-synthesized anti-tumor drug that actively seeks the acidic tumor microenvironment while ignoring the normal tissue without the aid of additional carriers. This called “carrier-free” drug (CFD) is capable of switching its morphology from the unstructured solution to the spherical structure in response to tumor acidity. CFDs were the water-soluble zwitterionic unimers to prevent the non-specific distribution in the circulation, whereas they spontaneously formed into the particles tending to accumulation in tumor. CFD overloading in tumor cells caused the lysosomal dysfunction and autophagy blockage, thereby triggered the cell death . All the in vitro and in vivo data demonstrated the tumor-acidity-selective cytotoxicity of CFD. This facile strategy to create a self-delivering anticancer drug may cast a new light on the development of cancer therapy.

Silica based click-dibenzo-18-crown-6-ether high performance liquid chromatography stationary phase and its application in separation of fullerenes

Yanzhe Li,Zhe Sheng,Chuanlei Zhu,Wei Yin,Changhu Chu

Crown ether is a type of typical macrocyclic polyether compounds, which can produce strong interactions with cationic species, such as metal ions and protonated amines due to its cavity structure and the strong electronegative effect of heteroatoms on the crown ether ring. In this paper, a type of silica based crown ether stationary phase was prepared by covalently bonding dibenzo-18-crown 6-ether (DBCE) on silica gel via copper (I) catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). The tetraazido DBCE was rapidly prepared by bromomethylation and subsequent azido substitution of DBCE. Finally, this key intermediate was covalently bonded to silica beads by click chemistry to get click-DBCE. Its structure was confirmed by FT-IR and elemental analysis, and the structures of all related intermediates were confirmed by NMR, IR and MS spectra. The crown ether based stationary phase showed good chromatography characteristics and column efficiency (up to 43,553 plates m -1 theoretical plate number is obtained in the case of fluoranthene) under reverse phase liquid chromatographic (RPLC) model. The primary chromatographic evaluation showed that click-DBCE displayed better chromatography efficiency than commercial C18 stationary phase (THERMO BDS HYPERSIL), when they were applied in the separation of regio-isomers of benzene, polycyclic aromatic hydrocarbons (PAHs) and macrolide pharmaceuticals. Furthermore, this stationary phase could also be used to separate fullerenes under normal phase mode, and in this case, 1-chloronaphthalene was suitable additive for improving chromatographic separation ability.

A thermo-sensitive OEGMA-based polymer: synthesis, characterization and interactions with surfactants in aqueous solutions with and without salt

Guo Yi,Dong Xiuyan,Ruan Wenjing,Shang Yazhuo,Liu Honglai

The interactions between poly(2-(2-methoxyethoxy)ethyl methacrylate 90 -co-oligo(ethylene glycol) methacrylate 10 ) (P(MEO 2 MA 90 -co-OEGMA 10 )) and sodium dodecyl sulfate (SDS) or dodecyltrimethyl ammonium bromide (DTAB) in aqueous solutions with and without salt are explored. The influence rule of surfactant on thermo-sensitive behavior of polymer and the corresponding mechanism is revealed. The results have suggested that both surfactants have moderate interactions with P(MEO 2 MA 90 -co-OEGMA 10 ), which result in the formation of P(MEO 2 MA 90 -co-OEGMA 10 )/surfactant complexes. Meanwhile, the self-aggregation of polymer chains is hindered causing the lower critical solution temperatures (LCSTs) increase due to the electrostatic repulsion and “locking water” effect caused by surfactant head groups. Tetra-n-butylammonium bromide (Bu 4 NBr) and tetra-n-propylammonium bromide (Pr 4 NBr) can associate with SDS and form mixed micelles. Interestingly, the formed mixed micelles apt to attach on the polymer chain and the polymer-bound necklace-like structure forms in the ternary polymer/salt/surfactant system. The structure of the complexes formed in the ternary system is confirmed by 2D NOESY NMR and the interaction mode is proposed. The relations between LCST of different systems and surfactant concentrations are also established quantitatively.

Preparation of pH-sensitive zwitterionic nano micelles and drug controlled release for enhancing cellular uptake

Luyan Wu,Caihua Ni,Liping Zhang,Gang Shi

Trackable Mitochondria-Targeting Nanomicellar Loaded with Doxorubicin for Overcoming Drug Resistance

Ye Zhang,Congjun Zhang,Jing Chen,Li Liu,Mengyue Hu,Jun Li,Hong Bi

Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.

Synthesis and in vitro evaluation of pH-sensitive PEG-I-dC16 block polymer micelles for anticancer drug delivery

Rongbin Huang,Lei Xiang,Ying Liu,Xiangping Deng,Xuan Cao,Lanfang Li,Cuiyun Yu,Yanming Chen,Guotao Tang

ObjectivesTo develop an acid trigger release of antitumour drug delivery carriers, pH-sensitive amphiphilic poly (ethyleneglycol)-imine-benzoic-dipalmitate (PEG-I-dC16) polymers were designed and synthesized and the drug-loaded micelles were evaluated in vitro.MethodsPEG-I-dC16 synthesized by Schiff base synthetic method and characterized by 1H-NMR. To determine the drug-loading capacity, doxorubicin (DOX) was encapsulated in the micelles using membrane dialysis method. Zeta potential, particle size, drug-loading capacity, in vitro drug release in different pH conditions and cytotoxicity evaluation of micelles were carried out comparing with non-acid liable PEG–amide–benzoic–dipalmitate (PEG-A-dC16) polymers micelles. The cellular uptake and intracellular distribution of DOX were detected by flow cytometry and confocal laser scanning microscope.Key findingsDrug-loading capacity and encapsulation efficiency of micelle (PEG molecular weight 2k) were 12.7 ± 1.1% and 49.8 ± 2.2%, respectively. The average particle size was 72.3 ± 2.5 nm. The DOX release rate of PEG-I-dC16 micelles is much higher at pH 6.5 than at pH 7.4. DOX cellular uptake and nuclear accumulation of PEG-I-dC16 micelles were more efficiency than that of PEG-A-dC16 micelles.ConclusionThe pH-sensitive PEG-I-dC16 micelles could be a promising drug delivery system for anticancer drugs.

Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery

Chang Li,Yan Shen,Chunmeng Sun,Nihad Cheraga,Jiasheng Tu

To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.

Enhanced Scirpus triqueter phytoremediation of pyrene and lead co-contaminated soil with alkyl polyglucoside and nitrilotriacetic acid combined application

Chen Tingru,Liu Xiaoyan,Zhang Xinying,Hou Yunyun,Chen Xiao,Tao Kaiyun

Purpose This study aimed to evaluate the effect of combination of alkyl polyglucoside (APG) and nitrilotriacetic acid (NTA) on improving the efficiency of phytoremediation for pyrene and lead (Pb) co-contaminated soil by Scirpus triqueter . Materials and methods Seedlings of S. triqueter with a similar size and biomass (3 g/pot) were grown on 2-month aged soil contaminated with 184.5 mg kg −1 of pyrene and 454.3 mg kg −1 of Pb at pH = 8.3. After growth for 10 days, different doses of APG and NTA were added into the soil. After 60 days, the height of plants, Pb concentrations in plants, and pyrene amounts in soil were determined. Results and discussion Combined application of NTA and APG with lower dosage (1 + 1 g kg −1 soil and 1 + 2 g kg −1 soil) had no notable negative influence on the growth of S. triqueter . Moreover, significant synergy on Pb accumulation in S. triqueter was achieved with APG and NTA combined application. Besides, the dissipation of pyrene from soil after 60-day planting was increased in APG and NTA treatments when compared with the control treatments. Application of APG alone or combined with NTA had greater effect on enhancing dissipation of pyrene from soil than NTA alone. Conclusions This study demonstrated that the remediation of Pb and pyrene co-contaminated soil by S. triqueter can be enhanced by combined application of APG and NTA. Long-term evaluation of this strategy is needed in co-contaminated field sites.

Study on the self-assembly properties of surface active hydrophobically associating polyacrylamide with nonionic surfmer units

Li Fan,Luo Yue,Hu Pan,Su Gaoshen

A novel class of hydrophobic associated copolymers (PASC) with nonionic surfmer was synthesized. These copolymers are the copolymerization product of acrylamide (AM), 2-(acrylamido)-2- methyl propane sulfonic acid (AMPS) and different contents of nonionic surfmer (CP). Macroscopic and microscopic self-assembly associative properties in solutions of PASC, as well as the effects of salt and temperature on the associative behavior were studied via viscosimetry, scanning electron microscope (SEM), atomic force microscope (AFM), rheology and fluorescence spectroscopy (FS). The results show that the introduced nonionic surfmer along polymer chain can lead to a strong intermolecular hydrophobic association in water. The viscosity and surface activity increased with the increase of polymer concentration and nonionic surfmer concentration. Additionally, the polymer showed a good thermal stability and good salt tolerance. Contact angle studies shows that PASC solution has good potential on change of wettability from oil-wet to water-wet. All of these properties indicate that the polymer is an excellent chemical for chemical enhanced oil recovery.

Evaluation of the antibacterial activity of a cationic polymer in aqueous solution with a convenient electrochemical method

Wang Yihong,Guo Qing,Wang Huafu,Qian Kun,Tian Liang,Yao Chen,Song Wei,Shu Weixia,Chen Ping,Qi Jinxu

Quaternized chitosan is a cationic biopolymer with good antibacterial activity, biocompatibility, and biodegradability, and it has been widely applied in many fields. We have developed a convenient method to evaluate the antibacterial activity of hydroxypropyltrimethylammonium chloride chitosan (HACC) with a nonionic surfactant poloxamer in aqueous solution by monitoring the change of the oxidation peak current in cyclic voltammetry. Increasing values of the oxidation peak current were positively correlated with the antibacterial activity of HACC–poloxamer solutions. Optical microscope images, the zeta potential, and fluorescence spectroscopy showed that the aggregation state of HACC–poloxamer was related to the ratio of the two polymers and also to the antibacterial activity and oxidation peak current. At an HACC-to-poloxamer ratio of 1:0.75, the maximum surface charge density and the smooth edge of HACC–poloxamer aggregates can accelerate diffusion in aqueous solution. It is expected that this convenient method can be applied for a quick evaluation of the antibacterial activity of cationic biopolymers in aqueous solution. The cyclic voltammograms of MB in HACC/poloxamer solution, and the antibacterial efficiency against S. aureus after incubated with HACC ( a ) and 1/0.75 of HACC/poloxamer ( b )

Phytoremediation effect of Scirpus triqueter inoculated plant-growth-promoting bacteria (PGPB) on different fractions of pyrene and Ni in co-contaminated soils

Xiao Chen,Xiaoyan Liu,Xinying Zhang,Liya Cao,Xiaoxin Hu

At present, few reveal the mechanism of inoculation plants with PGPB to remediate PAH-metal co-contaminated soil by analyzing the chemical speciations of contaminants. This study investigated the influence of inoculation plants with PGPB on different fractions of pyrene and Ni in rhizospheric and non-rhizospheric soil. The results demonstrated that the addition of PGPB brought the extensive increase of FDA activities in pyrene-Ni co-contaminated soil. PGPB increased the resistance of plants in nickel and pyrene-Ni contaminated soil, but decreased the plant biomass in single pyrene contaminated soil. The addition of PGPB efficiently decreased bioaccessible fractions of pyrene and increased the bioavailability of Ni in both rhizospheric and non-rhizospheric soil. Although inoculation plants with PGPB significantly increased the accumulation of Ni in single Ni and pyrene-Ni co-contaminated soil, the poor bioavailability of Ni in rhizospheric soil still restricted the phytoremediation of the heavy metal. The presence of pyrene hindered the inoculated plant from accumulating Ni to some extent. On the contrary, the presence of Ni significantly promoted the degradation of pyrene in both rhizospheric and non-rhizospheric soil after inoculation plants with PGPB.

Biodegradation of phenanthrene by Rhizobium petrolearium SL‐1

Huang X.,Shi J.,Cui C.,Yin H.,Zhang R.,Ma X.,Zhang X.

AimsWe aimed to investigate the phenanthrene degradation characteristics and possible phenanthrene degradation pathways of Rhizobium petrolearium SL‐1.Methods and ResultsUsing high‐performance liquid chromatography (HPLC), UV‐visible and gas chromatography‐mass spectrometry (GC‐MS) analysis, the phenanthrene‐degrading properties and metabolites of Rh. petrolearium SL‐1 were analysed, and then combined with genome‐based analysis to elucidate the possible biodegradation pathway of phenanthrene in Rh. petrolearium SL‐1. The results of the analyses showed that phenanthrene (100 mg l−1) was completely degraded by strain SL‐1 at 35°C, 0·02% salinity and pH 9·0 within 3 days. A wide range of polycyclic aromatic hydrocarbons, including naphthalene, fluorene, anthracene and pyrene, could also be degraded by this strain.ConclusionsBased on the identified metabolites, the utilization of probable intermediates and the presence of putative phenanthrene catabolic genes, we concluded that phenanthrene was degraded via two different routes, namely the ‘naphthalene’ and the ‘phthalic acid’ routes.Significance and Impact of the StudyFor the first time, this study shows the degradation pathway of phenanthrene by a Rhizobium strain. Because of its excellent stress resistance, metabolic versatility, high degradation efficiency and potential application in phytoremediation, Rh. petrolearium SL‐1 is a potential candidate for the bioremediation of polycyclic aromatic hydrocarbons‐contaminated areas.