COLLOIDS AND SURFACES B-BIOINTERFACES
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2014
·
IF 4.287
Lili Zhang,Zeyou Qi,Qiyu Huang,Ke Zeng,Xiaoyi Sun,Juan Li,You-Nian Liu
To enhance the solubility and improve the bioavailability of hydrophobic curcumin, a new kind of imprinted-like biopolymeric micelles (IBMs) was designed. The IBMs were prepared via co-assembly of gelatin–dextran conjugates with hydrophilic tea polyphenol, then crosslinking the assembled micelles and finally removing the template tea polyphenol by dialysis. The obtained IBMs show selective binding for polyphenol analogous drugs over other drugs. Furthermore, curcumin can be effectively encapsulated into the IBMs with 5 × 10 4 -fold enhancement of aqueous solubility. We observed the sustained drug release behavior from the curcumin-loaded IBMs (CUR@IBMs) in typical biological buffers. In addition, we found the cell uptake of CUR@IBMs is much higher than that of free curcumin. The cell cytotoxicity results illustrated that CUR@IBMs can improve the growth inhibition of HeLa cells compared with free curcumin, while the blank IBMs have little cytotoxicity. The in vivo animal study demonstrated that the IBMs could significantly improve the oral bioavailability of curcumin.
研究领域:
药剂学
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纳米技术
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2014
·Vol. 3
·期 3
·490-499
·
IF 0
Gongyan Liu,Quanqing Luo,Haiqi Gao,Yuan Chen,Xing Wei,Hong Dai,Zongcai Zhang,Jian Ji
In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.
研究领域:
药学
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生物材料
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
Nano Research
·
2014
·Vol. 8
·期 2
·491-501
·
IF 6.963
Shen Liangliang,Zhao Lizhi,Qu Rui,Huang Fan,Gao Hongjun,An Yingli,Shi Linqi
A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)- block poly(4-vinylpyridine- co - N -heptyl-4-vinylpyridine) (PEG- b -P(4VP- co -4VPHep)), tetrakis(4-sulfonatophenyl)porphinato iron(II) (Fe(II)TPPS) and β-cyclodextrin (β-CD). The μ-oxo dimer of Fe(II)TPPS was successfully inhibited because the Fe(II)TPPS was included into the cavities of β-CDs through host-guest interaction. Fe(II)TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion (β-CD/Fe(II)TPPS) was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe(II)TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S 2 O 4
2− ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts (Fe(II)TPPS(O 2 )) were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O 2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.
研究领域:
生物材料学
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仿生学
·
医学工程
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DOI
高影响因子
ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
研究领域:
药学
·
癌症研究
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhang Lan,Tan LiWei,Chen LiJuan,Chen XiaoXin,Long ChaoFeng,Peng JinRong,Qian ZhiYong
Self-assembled polymeric micelles have been widely applied in drug delivery systems. In this study, we found that pH value of micellar system solution was the decisive factor of physical stability. Furthermore, the weak basic solution could maintain the solution clarification for a relative long time. To investigate the stability of polymeric micelles in different pH solutions, the micellar particle size and the docetaxel content remaining in solution were detected at predetermined time points. The crystallographic assay of freeze-drying powder was characterized by an X-ray diffractometer. In vitro release results indicated that the PBS had little influence on the sustained-release effect of docetaxel-loaded polymeric micelles (DPM). Besides, the safety of micellar formulation was determined by an MTT assay on HEK293 cells, and the anti-tumor activity was tested on MCF-7 cells. The results demonstrated that DPM adjusted with PBS (DPM (PBS)) was of low toxicity and maintained the effectiveness of docetaxel. In vivo antitumor results indicated that DPM (PBS) had better antitumor efficacy than common docetaxel injection (DTX). Thus it was concluded that regulation of micellar solution PH by PBS is a safe and effective method to improve the physical stability of DPM. It might promote the application of micellar formulation in clinical applications.
研究领域:
药剂学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2015
·
IF 1.648
Ju Liang,Wenlan Wu,Danyu Lai,Junbo Li,Cailin Fang
A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 103 times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.
研究领域:
药剂学
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2015
·
IF 4.457
Ruidong Cheng,Min Tian,Sujuan Sun,Chenghui Liu,Youpeng Wang,Zhaotie Liu,Zhongwen Liu,Jinqiang Jiang
The amphiphilic random copolymer of P(NVP-co-NHPSS) with photocleavable N–O sulfonate side groups has been prepared to investigate the light-triggered disruption of copolymer micelles. Methods of absorption and emission spectra, solution transmittance, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were applied. It was found that P(NVP-co-NHPSS) could form polymeric nanoaggregates in aqueous solution. And the photocleavage of the N–O bond within copolymer micelles upon 365 nm UV light could be conveniently controlled by changing the irradiation intensity, leading to the disruption of copolymer micelles and the photocontrolled release of Nile red encapsulation. And by encapsulating NaLuF4:Gd/Yb/Tm UCNPs inside copolymer micelles, the response of the photocleavable N–O bond to the 980 nm laser was much weaker than the response to 365 nm light; however, the photocontrolled release of Nile red could still be effectively triggered by the NIR light of the 980 nm laser.
研究领域:
材料科学
·
化学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 42
·35658-35667
·
IF 3.289
Lingling Zhao,Yajuan Zhang,Jia Shao,Hongze Liang,Haining Na,Jin Zhu
Phenylboronic acid and folate grafted chitosan hydrochloride (FHCSPBA) was synthesized and confirmed by FTIR and 1H NMR. Glucose and pH dually responsive micelles were obtained through self-assembly of the amphiphilic polymers. The prepared FHCSPBA micelles displayed good biocompatibility and sustained drug release of the model drug doxorubicin hydrochloride (DOX). The cumulative drug release from the polymeric micelles showed obvious pH and glucose dependence and was accelerated by slightly decreasing the medium pH or increasing the glucose concentration. In vitro antitumor efficiency was evaluated by incubating the DOX loaded micelles with 4T1 breast cancer cells, and the results showed that folate-targeted micelles had higher antitumor activity than the non-targeted ones. Cellular uptake demonstrated by confocal microscopy indicated that free DOX was internalized in the nuclei of 4T1 cells, while the DOX loaded micelles were internalized in the cytoplasm. The cellular uptake of the micelles was enhanced by folate, with stronger fluorescence intensity in the cytoplasm, due to active FR-mediated endocytosis. These folate-conjugated glucose and pH dually responsive micelles may be a potential antitumor drug delivery system for cancer chemotherapy.
研究领域:
药剂学
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肿瘤学
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生物材料
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产品关联
DOI
高影响因子
Polymer Chemistry
·
2017
·Vol. 8
·期 16
·2472-2483
·
IF 5.375
Shuai Li,Yuanyuan Cai,Jun Cao,Mengtan Cai,Yuanwei Chen,Xianglin Luo
Micelles with phosphatidylcholine surfaces have numerous advantages, such as good biocompatibility and high enrichment of drug in tumor tissue. In this study, we developed hyaluronic acid-coated phosphatidylcholine micelles, prepared via electrostatic attraction, for targeting the delivery of doxorubicin (DOX) to tumors. An amphiphilic copolymer poly(caprolactone)-poly(N,N-diethylaminoethyl methacrylate)-r-poly(2-(methacryloyloxy) ethyl phosphoryl choline) (PCL-PDEAMPC) was designed and synthesized successfully. PCL-PDEAMPC micelles and their DOX-loaded micelles were prepared by the dialysis method and were coated with hyaluronic acid (HA). The results showed that the micelle diameters increased a little and the zeta potential changed from positive to negative after coating with HA. The in vitro DOX release from phosphatidylcholine micelles could be triggered by pH, and the release from HA-coated PCL-PDEAMPC micelles was slower than that from PCL-PDEAMPC micelles. The in vitro cytotoxicity of the micelles was investigated using the MTT method in 4T1 cells. The results showed that the half maximal inhibitory concentration (IC50) of PCL-PDEAMPC-HA/DOX micelles was lower than that of PCL-PDEAMPC/DOX micelles. The CLSM images of cellular uptake indicated the ability of these micelles to enter into 4T1 cells. The experiments of in vivo antitumor effect and safety evaluation of DOX-loaded micelles demonstrated that the HA-coated DOX micelles had a better treatment effect and lower toxicity to 4T1-bearing Kunming mice. HA-decorated PCL-PDEAMPC micelles are therefore potential carriers for 4T1 tumor treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 73
·45978-45986
·
IF 3.108
Na Wen,Chunmei Gao,Shaoyu Lü,Xiubin Xu,Xiao Bai,Can Wu,Piao Ning,Shaofei Zhang,Mingzhu Liu
The high pKa (8.26 to 8.6) of PBA has restricted its glucose-responsiveness in physiological conditions, and the high cytotoxicity of polymers is also a limiting problem in their potential application for insulin delivery. Novel amphiphilic glucose-sensitive dialdehyde starch polymers containing 3-aminophenylboronic acid (APBA) as a glucose-responsive group and mPEGylated dialdehyde starch (mPEG-DAS) with hydrophobic 7-hydroxycoumarin-4-acetic acid (Cou) were synthesized. This dialdehyde starch derivative can self-assemble into mPEG-DAS–APBA–Cou micelles with “shell–core” structures in phosphate-buffered saline solution (PBS). In addition, the drug-loaded micelles can release insulin rapidly in response to hyperglycemia in a physiological environment. The results demonstrated that the mPEG-DAS–APBA–Cou micelles showed notable glucose responsive behavior near the physiological range. The insulin release from the nanocarriers is sensitive to different concentrations of glucose, releasing insulin rapidly under the conditions of 3 mg mL−1 glucose while demonstrating comparatively inert release at 1 mg mL−1 glucose (pH 7.4). MTT assays and hemolysis studies both confirmed that the mPEG-DAS–APBA–Cou micelles have low cytotoxic activity to A549 cells and low blood toxicity. These results suggest that the glucose-sensitive dialdehyde starch micelles (mPEG-DAS–APBA–Cou) have potential applications as a glucose-responsive material for insulin delivery.
研究领域:
药学
·
纳米技术
·
生物材料
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
FOOD HYDROCOLLOIDS
·
2020
·
IF 7.053
Qing Liu,Fang Li,Na Ji,Lei Dai,Liu Xiong,Qingjie Sun
Natural amphiphilic polymer micelles are of great interest as a carrier of hydrophobic functional ingredients due to their relatively easy synthesis, biocompatibility, and extensive sources. This study modified debranched starch (DBS) with acetic anhydride to introduce the hydrophobic acetyl group, and micelles were then obtained through the self-assembly of acetylated debranched starch (ADBS). The degree of substitution (DS) and the structural and thermal properties of ADBS were systematically investigated; the maximum DS value was 0.17. Proton nuclear magnetic resonance spectra of ADBS confirmed the presence of acetyl methyl protons, and Fourier transform infrared spectra exhibited a new absorption band of carbonyl C = O vibration at 1730 cm −1 due to the introduction of acetyl. The developed micelles were mostly spherical, and the particle size was about 50–100 nm. The critical micelle concentration was 0.45 mg/mL. Curcumin was incorporated into the micelles successfully, and the curcumin-loaded micelles exhibited sustained release properties in simulated gastric and intestinal fluids.
研究领域:
食品科学与工程
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Li Li,Bingjie Wang,Qi Zhang,Panpan Song,Tianze Jiang,Xia Zhao
Enhancing tumor reactive oxygen species (ROS) is a promising strategy for improved cancer chemotherapy. However, the high level of glutathione (GSH) in hypoxic tumor cells can neutralize ROS, restricting the application of ROS boosted therapy. Herein, hypoxia-responsive polymer micelles ( [email protected] ) were constructed to amplify intra-tumor oxidative stress to enhance the chemotherapeutic efficacy of doxorubicin (DOX). The amphiphilic polymer consists of hydrophilic fucoidan (Fuc) linked by azobenzene with hydrophobic linolenic acid (LA), and can self-assemble into micelles to encapsulate DOX. Under hypoxia, [email protected] decreased intratumoral GSH by consuming nicotinamide adenine dinucleotide phosphate (NADPH), and caused accumulation of lethal ROS and lipid peroxides, resulting in mitochondrial damage and enhanced anti-tumor performance of DOX. [email protected] (IC 50 1.685 μg/mL) improved the effect of DOX (IC 50 7.847 μg/mL) on hypoxic tumor cells by nearly 4.6-fold. The current work provides a novel strategy for enhancing the antitumor efficacy via oxidative stress augmented chemotherapy.
研究领域:
癌症研究
·
药学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）