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RSC Advances · 2014 ·Vol. 5 ·期 10 ·7433-7439 · IF 3.708

Fluorescence enhancement of fisetin by silver nanoparticles with cetyltrimethyl ammonium bromide micelles

Xiaodan Liu,Xia Wu

In this work, in situ synthesized cetyltrimethyl ammonium bromide micelles-capped silver nanoparticles were used to sensitively and directly detect fisetin. Fisetin molecules solubilize in the Stern layer of cetyltrimethyl ammonium bromide micelles and mainly bind to the head group of the micelles by electrostatic interaction and hydrophobic effect. Silver nanoparticles also solubilize in cetyltrimethyl ammonium bromide micelles and form the micelles-capped silver nanoparticles. The suitable distances between fisetin molecules and silver nanoparticles for the fluorescence enhancement are provided by the micelles. The synergistic action of the solubilization and sensitization of micelles and metal-enhanced fluorescence of silver nanoparticles promote the fluorescence enhancement of the system. Under optimized conditions, the fluorescence intensity of the system exhibits a linear response with the concentrations of fisetin in the range from 5.0 × 10−8 mol L−1 to 7.0 × 10−6 mol L−1 and the detection limit (S/N = 3) is 1.5 × 10−9 mol L−1. Compared to the other methods, the developed method has higher sensitivity. Moreover, the method has been successfully used to detect fisetin in actual samples.

研究领域: 分析化学 · 纳米技术 · 药物分析
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2015 · IF 3.65

Preparation and characterization of the ion-fixed mixed micelles with superior stability

Yang Li,Yang Fu,Hongyu Guo,Lixue Zhang,Lingling Huang,Li Yang

The inherent instability of micelles remains a main challenge for antitumor drug delivery, the objective of this study is to prepare and characterize the ion-fixed mixed micelles with significantly improved stability. The mixed micelles and ion-fixed mixed micelles combining the carboxy-containing PLA (PLA-COO − ) and mPEG-PLA were formed by inserting PLA-COO − into micellar core without and with metal ions , respectively. The critical micelle concentration (CMC) of mixed micelle depended on the origin PLA length in the mPEG-PLA, whereas kinetic stability of the mixed micelles was significantly improved, irrespective of the PLA length. However, curcumin (Cur)-loaded mixed micelles did not show higher physical stability upon dilution and Cur-micelle bonding constant due to the lower loading space. On the contrary, the ion-fixed mixed micelles formed in the presence of CaCl 2 solution showed a high physical stability upon dilution due to the solidification of micellar core by forming the more hydrophobic (PLA-COO − ) 2 Ca 2+ complex. The Cur-loaded ion-fixed mixed micelles showed the comparable cellular uptake of Cur and cytotoxicity in comparison with mPEG-PLA micelles. Our study highlights a universal combining strategy of ion-fixed mixed micelles with superior stability to individual micelles for antitumor drug delivery.

CAS / MDL: 9048-46-8 129-00-0
研究领域: 药剂学 · 生物医学工程
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JOURNAL OF APPLIED POLYMER SCIENCE · 2015 ·Vol. 132 ·期 31 · IF 1.768

Preparation of 2-(dimethylamino) ethyl methacrylate copolymer micelles for shape memory materials

Yan Yang,Funian Mo,Yangyang Chen,Yingyi Liu,Shaojun Chen,Jiandong Zuo

Researchers are actively developing shape memory polymers (SMPs) for smart biomaterials. This paper reports a new SMP system synthesized from biocompatible 2-(dimethylamino) ethyl methacrylate (DMAEMA), butyl acrylate (BA) and tri(ethylene glycol) divinyl ether (TDE). Preliminary results show that the DMAEMA-co-BA-co-TDE copolymers form micelles in aqueous solution due to chemical crosslinking and hydrophobicity. The micelle size decreased with the increase in the BA content since the hydrophobicity of copolymers increases with the increase of BA content. The resulting polymer films contain–N(CH 3 ) 2 functional groups for further biomaterial applications. The thermal stability of DMAEMA-co-BA-co-TDE copolymers is determined by the DMAEMA structure and content. Moreover, the copolymers form micro-phase-separated structures containing a reversible amorphous soft phase, and the storage moduli decreases significantly around T g . Therefore, good thermal-induced shape memory effects are achieved in the DMAEMA-co-BA-co-TDE copolymers by adjusting the BA content. This work proposes a new strategy for designing smart biomaterials using a biocompatible monomer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42312.

研究领域: 高分子化学 · 生物医学材料
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RSC Advances · 2015 ·Vol. 5 ·期 73 ·59056-59061 · IF 3.84

Colorimetric and fluorescent detection of GSH with the assistance of CTAB micelles

Lun Song,Haiyu Tian,Xiaoliang Pei,Ziyou Zhang,Weibing Zhang,Junhong Qian

Two water-soluble colorimetric and turn-on fluorescent probes STP1–2 were rationally designed and synthesized for selective recognition of GSH. Both probes are colorless 4-thioether-1,8-naphthalimide derivatives, which are almost non-fluorescent due to the photoinduced electron transfer from the fluorophore to the 4-nitrobenzene. Upon addition of GSH to STP1/STP2–CTAB solution, obvious spectral responses were observed: the absorption peak shifted from 345 nm to 390 nm companied with ∼90-fold fluorescence enhancement at 487 nm. A good linear relationship between the fluorescence intensity and GSH concentration was obtained, and the detection limit of GSH was estimated to be 8.40 × 10−8 mol L−1. The experimental results imply that both probes could be applied in fluorescent imaging of GSH within living cells and in the detection of mercapto-containing proteins as well.

研究领域: 生物化学 · 分析化学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2015 · IF 3.368

Bilayers and wormlike micelles at high pH in fatty acid soap systems

Wenlong Xu,Huizhong Liu,Aixin Song,Jingcheng Hao

Bilayers at high pH in the fatty acid systems of palmitic acid/KOH/H 2 O, palmitic acid/CsOH/H 2 O, stearic acid/KOH/H 2 O and stearic acid/CsOH/H 2 O can form spontaneously (Xu et al., 2014, 2015). In this work, the bilayers can still be observed at 25   °C with an increase of the concentration of fatty acids. We found that wormlike micelles can also be prepared in the fatty acid soap systems at high pH, even though the temperature was increased to be 50   °C. The viscoelasticity , apparent viscosity, yield stress of the bilayers were determined by the rheological measurements. Wormlike micelles were identified by cryogenic transmission electron microscopy (cryo-TEM) and emphasized by the rheological characterizations, which are in accordance with the Maxwell fluids with good fit of Cole–Cole plots. The phase transition temperature was determined by differential scanning calorimetry (DSC) and the transition process was recorded. The regulating role of counterions of fatty acids were discussed by (CH 3 ) 4 N + , (C 2 H 5 ) 4 N + , (C 3 H 7 ) 4 N + , and (C 4 H 9 ) 4 N + as comparison, concluding that counterions with appropriate hydrated radius were the vital factor in the formation wormlike micelles.

CAS / MDL: 1310-58-3
研究领域: 胶体化学 · 表面活性剂科学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2015 · IF 3.65

Intracellular Doxorubicin Delivery of a Core Cross-linked, Redox-responsive Polymeric Micelles

Yu. Lili,Mu. Ruihua,Li. Li,Liang. Fei,Yao. Lin,Su. Li

Redox-responsive micelles based on amphiphilic polyethylene glycol-polymethyl methacrylate with the introduction of disulfide containing cross-linked agent (mPEG-PMMA-SS) were developed for intracellular drug release. Benefiting from the amphiphilicity, mPEG-PMMA-SS could self-assembled into core cross-linked micelles in aqueous medium with tunable sizes (85–151   nm), appropriate zeta potential (−24.8   mV), and desirable critical micelle concentration (CMC) (0.18   mg/mL). Doxorubicin (DOX) could efficiently load into the micelles with satisfactory entrapment efficiency. As expected, the in vitro release studies displayed that DOX release from mPEG-PMMA-SS micelles was about 75% within 10   h under tumor-relevant reductive condition, whereas only about 25% DOX was released in non-reductive medium. SRB assays indicated that these mPEG-PMMA-SS micelles were biocompatible and nontoxic up to a concentration of 50   μg/mL. The cytotoxicity studies and the intracellular drug delivery demonstrated that the drug release behavior in cells was related to the concentration of GSH in cytoplasm. Furthermore, the cell experiments using fluorescence microscopy showed clearly that DOX was delivered by micelles to the cytoplasm, released in cytoplasm under reductive environment, and then accumulated in cell nucleus. These results suggest that such redox-responsive micelles may develop into an efficient cytoplasmic delivery for hydrophobic anticancer drugs .

研究领域: 药剂学 · 肿瘤学 · 生物材料
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JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY · 2017 ·Vol. 55 ·期 6 ·1021-1030 · IF 2.952

Morphological switching of unimolecular micelles of ternary graft copolymers in different solvents

Yangmiao Mo,Guojun Liu,Yuanyuan Tu,Shudong Lin,Jun Song,Jiwen Hu,Feng Liu

A series of ternary graft copolymers with poly(3-azido-2-hydroxypropyl methacrylate) (P(GMA-N 3 )) as the main chain, end-functionalized poly(ethylene glycol) methyl ether (MPEG), poly( t -butyl acrylate) (PtBA), and poly(2-cinnamoyloxyethyl methacrylate) (PCEMA) as the side-chains, was synthesized via the combination of atom transfer radical polymerization (ATRP) and click chemistry. The formation of well-defined ternary graft copolymers was confirmed by both size exclusion chromatography (SEC) and 1 H NMR spectroscopy The loose and worm-like morphology of the ternary graft copolymer in a common solvent ( N , N -dimethylformamide) for both the backbone and the grafts was directly visualized via atomic force microscopy (AFM). The average height, width, and length of these solvated macromolecules were about 1.5, 17, and 45 nm, respectively. The ternary graft copolymers underwent self-assembly in different selective solvents (dichloromethane, methanol, and water) and thus yielded unimolecular micelles (UMs) with different morphologies. The morphological transitions in response to variations in the selective solvents was investigated by AFM as well as/or transmission electron microscopy (TEM). Experimental results showed that the micellar morphology of the ternary graft copolymer changed from a pearl-necklace to a worm-like structure and then to a spherical structure when the selective solvent was respectively changed from CH 2 Cl 2 to CH 3 OH and then to H 2 O. SEC characterization revealed that the compact globules formed in H 2 O with PCEMA/PtBA as the hydrophobic core arose due to intramolecular folding. Thus, multicompartment UMs were generated. The volume ratio of the multicompartment UMs formed in H 2 O was in close agreement with their molecular weight ratio. The hydrodynamic diameters ( D h ) of the acquired multicompartment UMs and their polydispersity indices were characterized by dynamic light scattering. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 1021–1030

研究领域: 高分子化学 · 材料科学 · 纳米技术
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2020 · IF 4.192

pH-Responsive Wormlike Micelles Formed by an Anionic Surfactant Derived from Rosin

Zhaolan Zhai,Shengfeng Ye,Xinyan Yan,Zhanqian Song,Shibin Shang,Xiaoping Rao,Jie Song

A novel pH-responsive wormlike micellar viscoelastic solution was constructed by a rosin-based anionic surfactant (Na-MPA-AZO-Na) in the presence of cetyltrimethylammonium bromide (CTAB). The viscoelasticity, aggregate morphology, and pH-responsiveness of the pH-responsive wormlike micelles have been investigated through the method of rheology and cryogenic-transmission electron microscopy. Its corresponding mechanism has been studied using 1H NMR and 1H–1H 2D NOESY HNMR. The zero-shear viscosity (η0) of the wormlike micellar solution rapidly decreases by 3 orders of magnitude as the pH increases from 5.21 to 9.56. The viscoelastic fluids and water-like solutions can be converted by tuning the pH between 3.62 and 12.00, and the corresponding aggregates also transform between wormlike micelles and spherical micelles. In addition, the wormlike micellar cross-sectional diameter is approximately 10 nm, which is remarkably larger than that of the common wormlike micelles. The phenomenon can be attributed to the large steric volume of the rosin rigid skeleton. When the pH is 12.00, a “pseudo” Gemini surfactant is constructed by Na-MPA-AZO-Na and CTAB through the electrostatic interactions. Wormlike micelles also can be formed with the increasing concentrations. The η0 of the wormlike micellar system shows strong dependence on concentration with an exponent of 9.6 (η0 ∝ C9.6). This work further promotes new applications of forest resources.

CAS / MDL: 57-09-0
研究领域: 材料科学 · 化学工程 · 生物医学
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Intracellular K+-Responsive Block Copolymer Micelles for Targeted Drug Delivery of Curcumin

Jiang Mingyue,Chen Le,Chen Bo,Yu Qinghua,Zhang Xianming,Jing Weihong,Ma Limei,Deng Tao,Yang Zhangyou,Yu Chao

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.

CAS / MDL: 78-67-1 1069-79-0
研究领域: 药学 · 纳米技术 · 癌症研究 · 材料科学
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Nanoscale · 2022 ·Vol. 15 ·期 1 ·365-375 · IF 8.307

Self-assembling ferrimagnetic fluorescent micelles for bioimaging guided efficient magnetic hyperthermia therapy

Yonghong Song,Yueqiang Zhu,Kun Jiang,Xingyu Liu,Liang Dong,Dongdong Li,Sheng Chen,Hanye Xing,Xu Yan,Yang Lu,Xianzhu Yang,Junxia Wang,Yunjun Xu

Multifunctional magnet–fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 诊疗学
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International Journal of Nanomedicine · 2022 · IF 7.033

Hyaluronic Acid Micelles for Promoting the Skin Permeation and Deposition of Curcumin

Jiangxiu Niu,Ming Yuan,Zhaowei Zhang,Liye Wang,Yanli Fan,Xianghui Liu,Xianming Liu,Huiyuan Ya,Yansong Zhang,Yang Xu

Background The poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs. Methods In this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed. Results The mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and −26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin. Conclusion CUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.

CAS / MDL: 124-30-1
研究领域: 药剂学 · 皮肤科学 · 生物材料
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2022 ·Vol. 23 ·期 18 ·10801 · IF 6.208

AIE-Featured Redox-Sensitive Micelles for Bioimaging and Efficient Anticancer Drug Delivery

Wei Zhao,Zixue Li,Na Liang,Jiyang Liu,Pengfei Yan,Shaoping Sun

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.Keywords:polymeric micelles;aggregation-induced emission;bioimaging;redox-sensitive;anticancer drug delivery

研究领域: 材料科学 · 生物医学工程 · 肿瘤学
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