查找使用阿拉丁产品的科研文献

In Vivo Biodistribution of Mixed Shell Micelles with Tunable Hydrophilic/Hydrophobic Surface

Hongjun Gao,Jie Xiong,Tangjian Cheng,Jinjian Liu,Liping Chu,Jianfeng Liu,Rujiang Ma,Linqi Shi

The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the 125I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.

Multi-responsive core-crosslinked poly (thiolether ester) micelles for smart drug delivery

Yanfang Hu,Ming Deng,Huailin Yang,Li Chen,Chunsheng Xiao,Xiuli Zhuang,Xuesi Chen

Herein, a kind of multi-responsive core-crosslinked poly (thiolether ester) micelles was facilely prepared for reactive oxygen species (ROS), acid and reduction sensitive drug delivery. Firstly, a hydroxyl-rich poly (thiolether ester) (PTE) was synthesized by the thiol-ene/thiol-expoxy polymerization using ethanedithiol (EDT) and glycidylmethacrylate (GMA) as monomers . The resultant PTE was then coupled with carboxyl terminated poly (ethylene glycol) (PEG) and lipoic acid (LA) to give the graft copolymer PTE- g -PEG-LA. The obtained PTE- g -PEG-LA could self-assemble into micelles in the aqueous media and turn into core-crosslinked nanoparticles in the presence of dithiothreitol (DTT) at pH ∼8.3.The core-crosslinked PTE- g -PEG-LA micelles showed more compact structure and higher drug loading efficiency towards the model drug doxorubicin (DOX) as compared with non-crosslinked PTE- g -PEG micelles. In vitro drug release profiles demonstrated that the release of drug from DOX-loaded core-crosslinked PTE- g -PEG-LA micelles (CNP/DOX) could be accelerated in the ROS-abundant, acidic or reductive environment. The triggered release of loading drug from CNP/DOX in A549 and HeLa cells were also verified by laser scanning confocal microscopy , flow cytometry and cell proliferation inhibition assessments. These results indicate that the cross-linked PTE- g -PEG-LA micelles may provide huge potential for smart drug delivery in cancer therapy.

Polyion complex micelles formed by azobenzene-based polymer with multi-responsive properties

Dandan Zhang,Jilu Li,Hongmei Xie,Aoqi Zhu,Yiting Xu,Birong Zeng,Weiang Luo,Lizong Dai

Compared with the single polymer micelle system, the polyion complex micellar system is consisted of two or more polymers with different composition, which has more flexible structural adjustment and better performance, making them widely used in drug control release. In this work, two azobenzene-based amphiphilic copolymers P (MMA- co -PEGMA- co -NIPAM- co -HAZOMA) with ionized carboxyl and P (MMA- co -PEGMA- co -NIPAM- co -NNAZOMA) with protonated tertiary amine group were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. We studied self-assembled behavior of polymers and multi-component polymers, including their multiple responsiveness and the encapsulation, controlled release properties of polyion complex micelle. Light, pH, temperature, and reduction responsiveness of three micelles were investigated by UV–vis spectroscopy, transmission electron microscope (TEM), and dynamic light scattering. Compared to RCP 1, and RCP 2, RCP 1/RCP 2 micelle can release Nile red in both acidic and alkaline environment. When temperature reached critical solution temperature, RCP 1/RCP 2 micelle would release Nile red faster. Polyion complex micelle had better release performance compared to single micelles at the same environment, and could release in a wider range pH, making it had more potential applications in biological science field.

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

Yishun Yang,Yuan Zhao,Jinshuai Lan,Yanan Kang,Tong Zhang,Yue Ding,Xinyu Zhang,Lu Lu

Introduction A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. Materials and methods HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. Results DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (−6.7 to −31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 μg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. Conclusion HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.

Synergistic effect of pH-responsive wormlike micelles based on a simple amphiphile

Xuepeng Wu,Yining Wu,Shuai Yang,Mingwei Zhao,Mingwei Gao,Hao Li,Caili Dai

Imagine a novel solution that can be switched reversibly from low viscosity to high viscosity with only one additive, upon different commands. To this end, we have developed a simple and effective route to form smart, multi-response wormlike micelles based on a synthesized surfactant, N-cetyl-N,N-diisopropanolammonium bromide (CDIAB). Moreover, we provide new insight into the effects of synergy on this smart wormlike micelle. Rheological measurements were used to study the morphology of the wormlike micelles; 1H NMR spectroscopy and density functional theory (DFT) calculations were employed to investigate the molecular arrangements and mechanism of the synergy involved in the reversible reactions of pH-response and CO2-response of the micelles in solution. Based on the abovementioned results, it is encouraging to discover that binding energy and electrostatic interaction are the basic driving forces in the formation of wormlike micelles. Moreover, stable viscoelastic behavior was observed in the CDIAB system, with strong binding energy and electrostatic interactions. It is highly anticipated that the synergy observed in this surfactant will be of particular interest due to its novel mechanism and unique properties.

AFM Studies on Liquid Superlubricity between Silica Surfaces Achieved with Surfactant Micelles

Jinjin Li,Chenhui Zhang,Peng Cheng,Xinchun Chen,Weiqi Wang,Jianbin Luo

By using atomic force microscopy (AFM), we showed that the liquid superlubricity with a superlow friction coefficient of 0.0007 can be achieved between two silica surfaces lubricated by hexadecyltrimethylammonium bromide (C16TAB) solution. There exists a critical load that the lubrication state translates from superlow friction to high friction reversibly. To analyze the superlow friction mechanism and the factors influencing the critical load, we used AFM to measure the structure of adsorbed C16TAB molecules and the normal force between two silica surfaces. Experimental results indicate that the C16TAB molecules are firmly adsorbed on the two silica surfaces by electrostatic interaction, forming cylinder-like micelles. Meanwhile, the positively charged headgroups exposed to solution produce the hydration and double layer repulsion to bear the applied load. By controlling the concentration of C16TAB solution, it is confirmed that the critical load of superlow friction is determined by the maximal normal force produced by the hydration layer. Finally, the superlow friction mechanism was proposed that the adsorbed micellar layer forms the hydration layer, making the two friction surfaces be in the repulsive region and meanwhile providing excellent fluidity without adhesion between micelles.

A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery

Jie Mao,Yang Li,Tong Wu,Conghui Yuan,Birong Zeng,Yiting Xu,Lizong Dai

To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4-formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ∼ 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.

Poly (Thioether-Polyesters) Micelles Encapsulation Induces ROS-Triggered Targeted Release of Tangeretin

Bozhan Tan,Zhiwen Qi,Guliang Yang,Haiyan Zhong

Tangeretin (Tan) possesses great anti-oxidation and anti-inflammation bioactivities; however, it is accompanied by poor water solubility, which leads to inefficient cellular internalization. To address this issue, a reactive oxygen species (ROS)-triggered poly (thioether-polyesters) micelle (PDHP, PEG-DTT) was designed and prepared via self-assembly, which consisted of poly (thioether-polyesters) as the hydrophilic shell, and the drug Tan as the hydrophobic inner core. The micelles (Tan@ PDHP), with a 63.15% loading efficiency of Tan, showed negligible cytotoxicity, high stability in phosphate-buffered saline buffer (pH  =  7.4), and continuous release of Tan with the stimulation of H2O2. In addition, this Tan loading micelle was more efficient in responding to the formation of ROS in the lipopolysaccharide-stimulated RAW264.7 cells compared to that of the free Tan. In short, the strategy of encapsulating the low solubility Tan in ROS-triggered poly (thioether-polyesters) micelles provides an effective assay of enhancing Tan's antioxidative activity.

Dual Thermo- and Photo-Responsive Micelles Based on Azobenzene-Containing Random Copolymer

Chuan Yan,Liqin Yang,Xiangquan Mo,Keying Chen,Weiya Niu,Zhiju Zhao,Guanghua Li

Amphiphilic random copolymer poly(methacrylamido-azobenzene)-ran-poly(2-hydroxyethylacrylate) (PMAAAB-ran-PHEA) was synthesized via hydrolysis of poly(methacrylamido-azobenzene)-ran-poly[2-((2′-tetrahydropyranyl)oxy)ethylacrylate] (PMAAAB-ran-P(THP-HEA)), which was prepared by conventional radical polymerization. PMAAAB-ran-PHEA micelles were then prepared via dialysis method against water with DMF as solvent. The structure, morphology, size, and low critical solution temperature (LCST) of PMAAAB-ran-PHEA and its micelles were determined by1H-NMR, GPC, TEM, and DLS. The thermo- and photo-responsive behaviors of the resulting polymer micelles were investigated with Nile red as a fluorescence probe. The results showed that PMAAAB-ran-PHEA micelles were porous or bowl-shaped and its size was 135–150 nm, and its LCST was 55 °C whenFMAAABof the random copolymer was 0.5351; the hydrophobicity of the micellar core was changed reversibly under the irradiation of UV light and visible light without release of Nile red or disruption of micelles; the size and solubilization capacity of the micelles were dependent on temperature, and Nile red would migrate for many times between the water phase and the micelles, and finally increasingly accumulated during the repeated heating and cooling processes.Keywords:methacrylamido-azobenzene;2-hydroxyethylacrylate;amphiphilic random copolymer;micelles;Nile red;photo-/thermo-responsiveness

Mitochondria-targeted and pH-triggered charge-convertible polymeric micelles for anticancer therapy

Lingli Jin,Yanwen Xu,Fengjiao Chen,Dingle Yu,Hongze Liang,Zhenjiang Liang,Ziyu Liu,Haiyan Li,Junying Liu,Hui Tan,Lingling Zhao

Mitochondria-targeted and pH-triggered charge-convertible polymeric micelles (GPTD) were developed for doxorubicin (DOX) delivery and targeted anticancer therapy. GPTD surface was negatively charged under physiological pH (7.4), while it converted to positive charge under tumor pH (6.8). Sustained release of DOX from the drug loaded polymeric micelles was observed and the drug release was accelerated by decreasing the medium pH from 7.4 to 6.8. Cellular uptake by U251 glioma cells showed that GPTD can enhance the accumulation of polymeric micelles inside the mitochondria after charge-mediated cellular internalization and release DOX into the cellular interior. In vivo anticancer activity performed on glioma Balb/c nude mice demonstrated that the DOX-containing GPTD could remarkably inhibit the tumor growth, and displayed a significant reduction of tumor tissue cells and fewer Ki67 positive cells compared to the PBS group. Hence, this mitochondrial targeted and pH-triggered charge-convertible polymeric micellar system showed substantial promise for anticancer therapy.

pH and temperature-responsive wormlike micelles formed by single amine oxide surfactant

Baogang Wang,Lei Liu,Cunchuan Zheng,Hongsheng Lu

Photo-induced dynamic association of coumarin pendants within amphiphilic random copolymer micelles

Chang Huan,Liu Yan,Shi Mei,Liu Zhaotie,Liu Zhongwen,Jiang Jinqiang

The water-soluble amphiphilic random copolymer of P(DMA- co -VBC) with coumarin pendants has been designed to investigate the photo-induced dynamic association of coumarin pendants within polymer micelles in aqueous solution. Methods of absorption and emission spectra, solution transmittance, dynamic light scattering (DLS), and atomic force microscope (AFM) were applied. It was found that P(DMA- co -VBC) can form polymer micelles in aqueous solution. The time-dependent photo-dimerization degree (PD) of polymer micelles upon different intensity irradiations of 320 nm light showed saturating behaviors with an intensity-independent value of the maximum photo-dimerization extent, while the maximum photo-cleavage extent of coumarin dimers declined with the increasing intensity of 254 nm irradiation at used conditions. Furthermore, a significant emission band at 445 nm ( I 2 ) evidently emerged as against the disappearance of emission band at 385 nm ( I 1 ) during the photo-dimerization, and the time-dependent I 2 /I 1 ratios of polymer aqueous solution upon alternative irradiations of 320 and 254 nm light showed a wave-like increase as a function of irradiation cycles, indicating a wavy closeness of coumarin pendants within polymer micelles during the reversible photo-dimerization cycles.