查找使用阿拉丁产品的科研文献

Photo-responsive, biocompatible polymeric micelles self-assembled from hyperbranched polyphosphate-based polymers

Chaojian Chen,Gongyan Liu,Xiangsheng Liu,Shaopeng Pang,Congshan Zhu,Liping Lv,Jian Ji

Photo-responsive biocompatible micelles were constructed from amphiphilic hyperbranched polyphosphate based polymer (denoted as HPHEEP-DNQ) and applied in the controlled release of coumarin 102. HPHEEP-DNQ was designed and synthesized by modification of hydrophilic hyperbranched polyphosphate (HPHEEP) with hydrophobic, light-responsive 2-diazo-1,2-naphthoquinone (DNQ) molecules. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements revealed that the polymer can self-assemble into spherical micelles with an average diameter of about 186 nm in aqueous solution. The critical micelle concentration (CMC) of the micelles was 0.025 mg mL−1 determined by fluorescence spectroscopy using Nile Red as a fluorescence probe. By illuminating the micelles with 365 nm UV light, light triggered destabilization procedure was investigated by TEM and DLS. In addition, model drug coumarin 102 was successfully encapsulated into the micelles and the controlled release behavior under 365 nm UV light was investigated by fluorescence spectroscopy. Cell viability tests against two types of cells indicated that the micelles have excellent biocompatibility. These photo-responsive and biocompatible polymeric micelles self-assembled from hyperbranched polyphosphate based polymer might have great potential as smart carriers in the field of drug delivery.

Dual and Multi-Emission Hybrid Micelles Realized through Coordination-Driven Self-Assembly

Youxiong Zheng,Yan Tang,Jianwei Yu,Lan Xie,Huiyou Dong,Rongsheng Deng,Fuhua Jia,Bingxin Liu,Li Gao,Junyuan Duan

Building novel functional nanomaterials with a polymer is one of the most dynamic research fields at present. Here, three amphiphilic block copolymers of 8-hydroxyquinoline derivative motifs (MQ) with excellent coordination function were synthesized by Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization. The coordination micelles were prepared through the self-assembly process, which the MQ motifs were dispersed in the hydrophobic polystyrene (PSt) blocks and hydrophilic Poly(N-isopropylacrylamide (PNIPAM)) blocks, respectively. The dual-emission micelles including the intrinsic red light emission of quantum dots (QDs) and the coordination green light emission of Zn2+-MQ complexes were built by introducing the CdSe/ZnS and CdTe/ZnS QDs in the core and shell precisely in the coordination micelles through the coordination-driven self-assembly process. Furthermore, based on the principle of three primary colors that produce white light emission, vinyl carbazole units (Polyvinyl Carbazole, PVK) with blue light emission were introduced into the hydrophilic PNIPAM blocks to construct the white light micelles that possess special multi-emission properties in which the intrinsic red light emission of QDs, the coordination green light of Zn2+-MQ complexes, and the blue light emission of PVK were synergized. The dual and multi-emission hybrid micelles have great application prospects in ratiometric fluorescent probes and biomarkers.

Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C

Xiu-Rong Zhang,Nian-Qiu Shi,Yang Zhao,He-Yun Zhu,Jiao Guan,Ying Jin

Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by 1H nuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

Jian Jin,Bowen Sui,Jingxin Gou,Jingshuo Liu,Xing Tang,Hui Xu,Yu Zhang,Xiangqun Jin

In this content, a small molecular ligand of prostate specific membrane antigen (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG) copolymers with different block lengths were synthesized to construct a satisfactory drug delivery system. Four different docetaxel-loaded polymeric micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm as characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Optimization of the prepared micelles was conducted based on short-term stability and drug-loading content. The results showed that optimized systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs with the same ratio of hydrophilic/hydrophobic chain length displayed similar sustained release behaviors. The cytotoxicity of the optimized targeted DTX-PCL 12K -PEG 5K -SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL 12K -mPEG 5K micelles (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that the targeted micelles had a much lower IC50 than their non-targeted counterparts (48 h: 0.87±0.27 vs 13.48±1.03 µg/ml; 72 h: 0.02±0.008 vs 1.35±0.54 µg/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence intensity than that of PMs1 after 4 h incubation. According to these results, the novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great promise for the treatment of prostatic cancer.

Visible-Light-Induced Diselenide-Crosslinked Polymeric Micelles for ROS-Triggered Drug Delivery

Xinfeng Cheng,Huixian Li,Xiaomeng Sun,Tianxu Xu,Zhenzhen Guo,Xianchao Du,Shuai Li,Xuyang Li,Xiaojing Xing,Dongfang Qiu

To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.

Micelles-Encapsulated with Azithromycin and Ibuprofen for Synergistic Antibacterial at Different pH

Feng Runliang,Chen Shiyu,Zhao Yingshun,Wang Mingzhu,Li Yuli,Jia Yunjing,Song Zhimei

Purpose To improve azithromycin’s antibacterial activity at different pH through combination therapy. Method Azithromycin- and ibuprofen-loaded micelles were fabricated by the self-assembly of MPEG-PVL copolymer, respectively. Results The drug-loaded micelles had controlled drug release property with water-solubility improvement. Notably, at pH 7.4 or 6.0, the in vitro antibacterial experiments demonstrated that there was no synergistic effect for the two native drugs against S. aureus , but a significant synergy was observed when the two preparations were used in combination. In vitro PI fluorescence staining experiment demonstrated that the introduction of ibuprofen-loaded micelles obviously increased cellular uptake under low concentration of azithromycin-loaded micelles. Through SEM and spectral evaluation experiments, it was found that ibuprofen-loaded micelles could increase the cell permeability by interacting with proteins and phospholipids in the cell membrane, which was conducive to promoting azithromycin-loaded micelles to enter the cells and play a drug effect. Conclusion The azithromycin- and ibuprofen-loaded micelles with synergistically enhanced antibacterial activity are potential candidates for effective bacterial combination therapy. Graphical Abstract

Manipulating Toughness and Microstructure in Polyelectrolyte Complex Hydrogels with Competitive Surfactant Micelles

Jiawen Hou,Xiaoliang Wang,Pingchuan Sun,Fenfen Wang

Polyelectrolyte complex (PEC) hydrogels provide a promising strategy to develop a class of physically cross-linked networks characterized by exceptional toughness and self-healing properties. However, the precise control of the microstructure and the enhancement of mechanical properties still pose challenges in the field of PEC hydrogels. Herein, we propose a strategy to manipulate the structure of PEC with competitively charged surfactant micelles, leveraging the spatially confined surface charge and excluded volume effects to overcome coacervation issues associated with the PEC, thus achieving a simple one-step preparation of macroscopically uniform and tough PEC hydrogels. Specifically, polyelectrolyte complex/surfactant micelle (PEC-SM) hybrid hydrogels were prepared by one-step copolymerization of chitosan (CS)/acrylic acid/cetyltrimethylammonium bromide (CTAB) micelles. The content of CTAB micelles was found to continuously modulate both the structure and the mechanical properties of the resulting PEC-SM hydrogel network. On one hand, reversible deformation-recovery behavior exhibited by CTAB cavity micelles through hydrophobic interactions efficiently dissipates energy; on the other hand, competition between CS chains and CTAB micelles for electrostatic binding sites with poly(acrylic acid), along with excluded volume effects of CTAB micelles, imparts a hierarchical structure upon the PEC-SM hydrogel. Rheology provided detailed insights into the viscoelastic behaviors of PEC-SM hydrogels at varying CTAB concentrations. The intermolecular interaction and heterogeneous network structure of physically cross-linked PEC-SM hydrogels with CTAB micelles were elucidated by solid-state nuclear magnetic resonance (NMR) spectroscopy. On the basis of rheology and NMR results, complemented by other characterization analyses, the physical illustration of the PEC-SM hybrid hydrogel network structure regulated by competitive surfactant micelles is presented. This work offers valuable in-depth insight into polyelectrolyte complexation and provides a foundation for the development of robust PEC hydrogel materials.

Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of osteoporosis

Yonghui Xie,Xueying Tan,Jian Huang,Hongwei Huang,Ping Zou,Jingbo Hu

Light/temperature dual-responsive ABC miktoarm star terpolymer micelles for controlled release

Haohui Huo,Xiaoyan Ma,YeQing Dong,Fengjin Qu

A novel light- and temperature-responsive amphiphilic ABC miktoarm star terpolymer consisting of hydrophilic poly(ethylene glycol) (PEG), light-responsive poly(2-nitrobenzyl methacrylate) (PNBM), and temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) arms, PEG(- b -PNBM)- b -PNIPAM, was synthesized via a combination of atom transfer radical polymerization (ATRP) and click reaction. In aqueous solution, the obtained miktoarm star terpolymer self-assembled into spherical micelles with PNBM cores and hybrid PEG/PNIPAM coronas. When heating above the phase transition temperature of PNIPAM, larger aggregates with mixed PNBM/PNIPAM cores and PEG coronas were formed. Upon UV light irradiation, the initial micelles were disrupted and reassembled into some large micelle complexes. Fluorescence emission measurements showed that Nile red encapsulated in the polymeric micelles could be released by stimuli of UV light or temperature change. More interestingly, the UV triggered release could be strengthened in basic conditions but weakened in acidic conditions. The prepared light- and temperature-responsive polymeric micelles may have great potential in applications such as nanocarriers and biotechnology for controlled drug and bioagent delivery.

Comparison of Biomimetic Block Copolymer Micelles as Drug Carriers for Cancer Therapy

Liu Gongyan,Chen Xiaobing,Zhuang Weihua,Nie Yu,Zhang Kai,Yang Li,Wang Yunbing

Zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is a promising alternative for poly(ethylene glycol) (PEG) as micelle shell-forming block. Three different PMPC-based polymeric micelles were designed and compared with PEGylated micelles. Cholesterol-conjugated and disulfide-modified poly(D, L-lactide)-SS-poly(2-methacryloyloxyethyl phosphorylcholine) (CPLA-SS-PMPC) micelles, cholesterol-conjugated CPLA-PMPC micelles without disulfides, and PLA-PMPC micelles without cholesterol-conjugation were compared to PLA-PEG micelles. These PMPC-based micelles showed better hydrophilicity and less protein adsorption. In cellular uptake evaluation, PMPC-based micelles exhibited much better cellular uptake than that of the PLA-PEG, which might reflect strong interaction between the biomimetic PMPC surface and the cellular membrane. In addition, although there was no statistical difference in cellular internalization behavior among these three PMPC-based micelles, the anticancer activity of paclitaxel (PTX)-loaded CPLA-SS-PMPC micelles was significantly higher than those of the other two kinds of micelles. This superiority was attributed to the rapid release of the anticancer drug under the redox environment inside cancer cells.

Synthesis, characterization and anti-cancer activity of Pluronic F68–curcumin conjugate micelles

Yuee Cai,Zhongqing Sun,Xiaobin Fang,Xiefan Fang,Fei Xiao,Yitao Wang,Meiwan Chen

Curcumin (CUR), a nontoxic polyphenol derived from the rhizome of turmeric (Curcuma longa), has been recognized as an anti-cancer and chemo-preventative agent. However, its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low bioavailability. To tackle this problem, Pluronic F68–CUR (F68–CUR) conjugate micelles, which are amphiphilic copolymers, were designed and synthesized in this study. These highly stable micelles with CUR concentrated in the core were formulated using the solvent evaporation method and were confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Physicochemical characterization of F68–CUR conjugate micelles revealed that high drug loading content (DL%; 0.248 mg CUR/1 mg F68) was achieved, and the average particle size of micelles was 115.2 ± 3.0 nm. Compared with free CUR, a significantly higher cytotoxicity against human breast cancer cell line MDA-MB-231 was observed in F68–CUR conjugate micelles. The IC50 value of F68–CUR conjugate micelles was 1.95-fold lower than that of free CUR, indicating that the anti-cancer activity of CUR was significantly improved in the micelles. Furthermore, apoptotic studies demonstrated that F68–CUR conjugate micelles induced more cell apoptosis than that of free CUR. Taken together, these results demonstrate that F68–CUR conjugate micelles are promising to improve the clinical effectiveness of CUR in cancer treatment.

Synthesis of the Hemoglobin-Conjugated Polymer Micelles by Thiol Michael Addition Reactions

Yanxin Qi,Taihang Li,Yupeng Wang,Xing Wei,Bin Li,Xuesi Chen,Zhigang Xie,Xiabin Jing,Yubin Huang

Amphiphilic triblock copolymers mPEG-b-PMAC-b-PCL are synthesized using methoxyl poly(ethylene glycol), cyclic carbonic ester monomer including acryloyl group, and ε-caprolactone. Copolymers are self-assembled into core–shell micelles in aqueous solution. Thiolated hemoglobin (Hb) is conjugated with micelles sufficiently through thiol Michael addition reaction to form hemoglobin nanoparticles (HbNs) with 200 nm in diameter. The conjugation of Hb onto the micelle surface is further confirmed by X-ray photoelectron spectroscopy. Feeding ratio of copolymer micelles to Hb at 1:3 would lead to the highest hemoglobin loading efficiency 36.7 wt%. The UV results demonstrate that the gas transporting capacity of HbNs is well remained after Hb is conjugated with polymeric micelles. Furthermore, the obtained HbNs have no obvious detrimental effects on blood components in vitro. This system may thus have great potential as one of the candidates to be developed as oxygen carriers and provide a reference for the modification of protein drugs.