查找使用阿拉丁产品的科研文献

PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking

Yajie Gao,Yanfang Li,Yushu Li,Lan Yuan,Yanxia Zhou,Jinwen Li,Lei Zhao,Chao Zhang,Xinru Li,Yan Liu

The cytotoxicity of chemotherapeutic agents to healthy organs and drug resistance of tumor cells are believed to be the main obstacles to the successful cancer chemotherapy in the clinic. To ensure that anticancer drugs could be delivered to the tumor region, are quickly released from carriers in tumor cells and rapidly escape from endo/lysosomes, YPSMA-1-modified pH-sensitive polymeric micelles, which would be advantageous in recognizing the prostate specific membrane antigen (PSMA), were designed and fabricated for targeted delivery of paclitaxel to tumors based on the pH-sensitive diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) and YPSMA-1-PEOz-PLA for treating prostate cancer. HOOC-PEOz-PLA with a critical micelle concentration of 5.0 mg L−1 was synthesized and characterized by 1H NMR and gel permeation chromatography. The prepared YPSMA-1-modified micelles, about 30 nm in diameter, exhibited a rapid release behavior at endo/lysosome pH and a favorable ability of fast endo/lysosome escape as observed by confocal microscopy. More importantly, we evidenced for the first time that both endosome and lysosome escape existed for pH-sensitive micelles via real time tracing using confocal microscopy, and the real time endo/lysosome escape process was also presented. The YPSMA-1-modified micelles were very effective in enhancing the cytotoxicity of paclitaxel by increasing the cellular uptake in PSMA-positive 22Rv1 cells, which was verified the correlation with PSMA expression in tumor cells by flow cytometric analysis and confocal microscopy. Moreover, the active targeting and pH-sensitivity endowed YPSMA-1-modified micelles with a higher antitumor efficacy and negligible systemic toxicity in 22Rv1 xenograft-bearing nude mice compared with unmodified micelles and Taxol®. These results suggested that the application of combining YPSMA-1 modification with pH-sensitivity to polymeric micelles may be one approach in the efficient delivery of anticancer drugs for treating PSMA-positive prostate cancers.

Effect of sodium alginate on the yogurt stability was dependent on the thickening effect and interaction between casein micelles and sodium alginate

Hongkai Zhang,Xiaofang Bian,Shunjing Luo,Chengmei Liu,Xiuting Hu

The effect of sodium alginate (SA) on the yogurt stability and the related mechanisms were investigated. It was found that low-concentration SA (≤0.2 %) increased the yogurt stability, while high-concentration SA (≥0.3 %) decreased the yogurt stability. Sodium alginate increased the viscosity and viscoelasticity of yogurt and this effect was positively correlated with its concentration, suggesting that SA worked as the thickening agent in yogurt. However, addition of ≥0.3 % SA damaged the yogurt gel. These results suggested that interaction between milk protein and SA might play an important role in the yogurt stability besides the thickening effect. Addition of ≤0.2 % SA did not change the particle size of casein micelles. However, addition of ≥0.3 % SA induced aggregation of casein micelles and increased the size. And the aggregated casein micelles precipitated after 3 h storage. Isothermal titration calorimetry analysis showed that casein micelles and SA were thermodynamically incompatible. These results suggested that the interaction between casein micelles and SA induced aggregation and precipitation of casein micelles, which was critical in the destabilization of yogurt. In conclusion, the effect of SA on the yogurt stability was dependent on the thickening effect and the interaction between casein micelles and SA.

Room-Temperature In Situ Synthesis of a Highly Efficient CsPbBr3/SiO2 Sol Entirely in Ethanol Solvent by Constructing Amine-Functionalized Silica Micelles

Jun Cheng,Shuanglong Yuan,Ludan Zhu,Long Chen,Chuanqi Liu,Hua Tong,Huidan Zeng

Cesium lead halide perovskite nanocrystals (CLHP NCs) have drawn considerable attention because of their promising optoelectrical properties. However, owing to the extreme vulnerability of CLHP NCs to water and polar alcohols, until now most synthesis approaches inevitably adopted ecounfriendly solvents. It is still a challenge to employ green polar alcohol (ethanol) as a solvent to synthesize CLHP NCs. In this work, we realized the room-temperature in situ synthesis of CsPbBr3/SiO2 sol entirely in ethanol by innovatively constructing amine-functionalized silica micelles, which originated from the synergistic effect of 3-aminopropyltriethoxysilane and tetraethylorthosilicate (TEOS) during an acid-catalyzed sol–gel process. The sol exhibited high stability and an absolute photoluminescence quantum yield of 61.9% in ethanol without a further modification process. The light-emitting intensity of the sol preserved for 34 days merely declined to 62.1%. This work sheds light on the less common strategy of directly synthesizing CsPbBr3 NCs and long-term stable preservation in a strongly polar solvent.

Core–Shell Structure, Biodegradation, and Drug Release Behavior of Poly(lactic acid)/Poly(ethylene glycol) Block Copolymer Micelles Tuned by Macromolecular Stereostructure

Chenlei Ma,Pengju Pan,Guorong Shan,Yongzhong Bao,Masahiro Fujita,Mizuo Maeda

Poly(ethylene glycol)-b-poly(l-lactic acid)-b-poly(d-lactic acid) (PEG-b-PLLA-b-PDLA) stereoblock copolymers were synthesized by sequential ring-opening polymerization. Their micelle formation, precise micelle structure, biodegradation, and drug release behavior were systematically investigated and compared with the PEG-b-poly(lactic acid) (PEG-b-PLA) diblock copolymers with various PLA stereostructures and PEG-b-PLLA/PEG-b-PDLA enantiomeric mixture. Stereoblock copolymers having comparable PLLA and PDLA block lengths and enantiomerically-mixed copolymers assemble into the stereocomplexed core–shell micelles, while the isotactic and atactic PEG-b-PLA copolymers formed the homocrystalline and amorphous micelles, respectively. The PLA segments in stereoblock copolymer micelles show smaller crystallinity than those in the isotactic and enantiomerically-mixed ones, attributed to the short block length and presence of covalent junction between PLLA and PDLA blocks. As indicated by the synchrotron radiation small-angle X-ray scattering results, the stereoblock copolymer micelles have larger size, micellar aggregation number, core radius, smaller core density, and looser packing of core-forming segments than the isotactic and enantiomerically-mixed copolymer micelles. These unique structural characteristics cause the stereoblock copolymer micelles to possess higher drug loading content, slower degradation, and drug release rates.

Microneedles incorporating oridonin micelles and Cu(II)-polydopamine provide effective inflammatory regulation and antibacterial effects for the healing of infected diabetic wounds

Wenbin Nan,Hao Wang,Linxiao Li,Jiulong Du,Xiangjuan Wei,Dongmei Wang,Yan Yang,Yongxue Wang,Dan Ding,Hongli Chen

The persistence of non-healing diabetic wounds is frequently attributed to excessive inflammation and bacterial infections. Therefore, strategies that target the reduction of inflammation while simultaneously inhibiting bacterial proliferation may offer an effective approach to overcoming this clinical challenge. In this study, we have developed an innovative formulation of hyaluronic acid (HA)-based dissolving microneedles (Cu(II)-PDA/ORI MNs) that incorporate oridonin (ORI) and Cu(II)-PDA nanoparticles, specifically designed for the treatment of chronic wounds in diabetic murine models. Our findings demonstrate that the composite MNs exhibit robust mechanical properties, facilitate drug delivery to the deeper layers of the skin, and exhibit favorable cytocompatibility and hemocompatibility. The encapsulation of ORI within the MNs effectively modulates the phenotype of RAW264.7 macrophages and exhibits significant anti-inflammatory properties, thereby contributing to the reduction of excessive inflammation within the wound microenvironment. Cu(II)-PDA nanoparticles significantly mitigate the toxicity associated with Cu(II) while retaining substantial antibacterial efficacy. Furthermore, they effectively promote wound angiogenesis, thereby expediting the wound healing process. Consequently, these Cu(II)-PDA/ORI MNs emerge as promising candidates for multifunctional wound dressing applications.

The CO2 stimulus-responsive spherical-worm-like micelles transition based on anionic surfactant sodium oleate and N, N, N′, N′, N″-pentamethyldipropylenetriamine

Hongsheng Lu,Youlin Ma,Baogang Wang,Zhiyu Huang

Somatostatin receptor-mediated tumor-targeting drug delivery using octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O, N-hydroxyethylation chitosan micelles

Meirong Huo,Aifeng Zou,Chengli Yao,Yong Zhang,Jianping Zhou,Jing Wang,Qinnv Zhu,Jing Li,Qiang Zhang

In this study, a ligand-PEG-lipid conjugate , octreotide-polyethene glycol-deoxycholic acid (OCT(Phe)-PEG-DOCA, or OPD) was successfully synthesized and used as a targeting molecule for N-deoxycholic acid-O, N-hydroxyethylation chitosan (DAHC) micelles for efficient cancer therapy. DAHC micelles exhibited good loading capacities for doxorubicin (DOX), a model anti-cancer drug, and the modification of OPD showed no significant effect on drug load while slightly increasing the particle size and partly shielding the positive charges on the surface of micelles. Accelerated release rate of DOX from micelles were also observed after OPD modification and the release profile exhibited pH-sensitive properties. Compared with DAHC-DOX micelles, OPD-DAHC-DOX micelles exhibited significantly stronger cytotoxicity to MCF-7 cells (SSTRs overexpression) but with hardly any difference from WI-38 cells (no SSTRs expression). The results of flow cytometry and confocal laser scanning microscopy further revealed that OPD-DAHC-DOX micelles could be selectively taken into tumor cells by SSTRs-mediated endocytosis . In vivo investigation of micelles on nude mice bearing MCF-7 cancer xenografts confirmed that OPD-DAHC micelles possessed much higher tumor-targeting capacity than the DAHC control and exhibited enhanced anti-tumor efficacy and decreased systemic toxicity. These results suggest that OPD-DAHC micelles might be a promising anti-cancer drug delivery carrier for targeted cancer therapy.

Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies

Xiaofei Wang,Qinyue Chen,Xiaoyan Zhang,Xiaoqing Ren,Xiulei Zhang,Lin Meng,Huihui Liang,Xianyi Sha,Xiaoling Fang

Background Improvement in drug accumulation in the lungs through inhalation administration and high expression of MMP2 and MMP9 in lung tumors have both been widely reported. Methods MMP2/9-triggered-release micelles were constructed and in vitro and in vivo studies of inhalation administration against lung tumor carried out. Pluronic P123 (P123) was modified with GPLGIAGQ-NH2 (GQ8) peptide to obtain P123-GQ8 (PG). MMP2/9-triggered-release micelles were constructed using PG and succinylated gelatin (SG) and loading paclitaxel (Ptx). To study biodistribution of micelles, DiR encapsulated in micelles was dosed to rats via intravenous injection or inhalation before ex vivo imaging for detecting DiR quantity in lungs. And B16F10 lung cancer-bearing nude mice were chosen as animal models to evaluate in vivo efficacy of MMP2/9-triggered-release micelles. Results Ptx-release efficiency from PG-SG-Ptx micelles was MMP2/9-concentration-dependent. For A549 cells, PG-SG-Ptx cytotoxicity was significantly greater ( P <0.001) compared to P123-Ptx. Aerosol inhalation was chosen as the method of administration. In biodistribution experiment, DiR quantity in lungs was 5.8%±0.4% of that in major organs, while the ratio was 38.8%±0.5% for inhalation. For B16F10 lung cancer-bearing nude mice, the efficacy of inhalation of PG-SG-Ptx was significantly higher ( P <0.001) than Taxol inhalation and injected PG-SG-Ptx. Inhaled PG-SG-Ptx also significantly inhibited the expression of Pgp in lung cancer. Conclusion Inhalation of MMP2/9-triggered-release micelles increased tumor sensitivity to chemotherapeutics and reduced the toxicity of chemotherapy to healthy lung cells, which has great potential in lung cancer therapy.

Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance

Xiaoqing Yi,Dan Zhao,Quan Zhang,Jiaqi Xu,Gongdao Yuan,Renxi Zhuo,Feng Li

Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

Effect of Hydrophobic Chain Length on the Stability and Guest Exchange Behavior of Shell-Sheddable Micelles Formed by Disulfide-Linked Diblock Copolymers

Haiyan Fan,Yixia Li,Jinxian Yang,Xiaodong Ye

Reduction-responsive micelles hold enormous promise for application as drug carriers due to the fast drug release triggered by reducing conditions and high anticancer activity. However, the effect of hydrophobic chain length on the stability and guest exchange of reduction-responsive micelles, especially for the micelles formed by diblock copolymers containing single disulfide group, is not fully understood. Here, shell-sheddable micelles formed by a series of disulfide-linked copolymer poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG–SS–PCL) containing the same chain length of PEG but different chain lengths of hydrophobic block PCL were prepared and well characterized. The influence of the chain length of hydrophobic PCL block on the stability and guest exchange of PEG–SS–PCL micelles was studied by the use of both dynamic laser light scattering (DLS) and fluorescence resonance energy transfer (FRET). The results show that longer PCL chains lead to a slower aggregation rate and guest exchange of micelles in the aqueous solutions containing 10 mM dithiothreitol (DTT). The cell uptake of the shell-sheddable PEG–SS–PCL micelles in vitro shows that the amount of internalization of dyes loaded in PEG–SS–PCL micelles increases with the chain length of hydrophobic PCL block investigated by flow cytometric analysis and confocal fluorescence microscopy.

Electrochemical determination of chloramphenicol in milk and honey using vertically ordered silica mesochannels and surfactant micelles as the extraction and anti-fouling element

Wenjing Zheng,Fei Yan,Bin Su

Chloramphenicol (CAP), an antibiotic, is closely related to the food safety, ecological environment and human health. It is therefore of great importance to develop simple and rapid methods for CAP determination. We report in this work the utilization of indium tin oxide (ITO) electrodes modified with a binary assembly of vertical silica mesochannels (VSMs) and cylindrical surfactant micelles (CSMs) for the electrochemical detection of CAP. Each hard VSM of 2–3   nm in diameter supports and confines a soft CSM of cetyltrimethylammonium bromide (CTAB), which has a hydrocarbon core capable of extracting and concentrating lipophilic organic analytes from sample solutions. So the CSM@VSM modified electrode exhibited an analytical performance for CAP apparently superior to bare and VSM modified electrodes. Under optimized conditions, two linear dynamic concentration ranges were obtained for CAP determination using differential pulse voltammetry , namely 0.1 to 3.6   ppm and 3.6 to 15.0   ppm, as well as a low limit of detection at 40   ppb. Moreover, thanks to the ultrasmall size of silica channels and the lipophilic microenvironment of micelle cores, the CSM@VSM film displayed an excellent hydrophobic selectivity and anti-fouling ability by preventing unwanted substances from accessing to and contaminating the underlying electrode surface . Therefore, reliable results were obtained for direct electrochemical determination of CAP in real samples, such as milk and honey, without pre-treatment.

CD44 Receptor-Targeted and Reactive Oxygen Species-Responsive H2S Donor Micelles Based on Hyaluronic Acid for the Therapy of Renal Ischemia/Reperfusion Injury

Xiudi Zhou,Qiang Chen,Chunjing Guo,Yanguo Su,Huimin Guo,Min Cao,Zhongxin Liu,Dandan Zhang,Ningning Diao,Huaying Fan,Daquan Chen

For the therapy attenuating renal ischemia–reperfusion (IR) injury, a novel drug delivery system was urgently needed, which could precisely deliver drugs to the pathological renal tissue. Here, we have prepared new nanomaterials with a reactive oxygen species (ROS)-responsive hydrogen sulfide (H2S) donor and hyaluronic acid that targets CD44 receptor. The novel material was synthesized and characterized via related experiments. Then, rapamycin was loaded, which inhibited kidney damage. In the in vitro study, we found that the micelles had ROS-responsiveness, biocompatibility, and cell penetration. In addition, the experimental results showed that the intracellular H2S concentration after administration was threefold higher than that of the control group. The western blot assay revealed that they have anti-inflammatory effects via H2S donor blocking the NF-κB signaling pathway. Consequently, the rising CD44 receptor-targeting and ROS-sensitive H2S donor micelles would provide a promising way for renal IR injury. This work provides a strategy for improving ischemia/reperfusion injury for pharmaceuticals.