RSC Advances
·
2017
·Vol. 7
·期 74
·47091-47098
·
IF 3.108
Yuling Liu,Longfei Lin,Jizheng Song,Ye Zhao,Zhimao Chao,Hui Li
Resveratrol (RES), a natural polyphenolic compound existing in plants, exhibits anticancer potential in inhibiting growth of various types of human cancers especially breast cancer. However, the poor aqueous solubility and low bioavailability limit its clinical application. Pluronic F127 (F127)-SS-Tocopherol (TOC) polymer is a redox-sensitive conjugate which has been synthesized by our previous study. Due to the amphiphilic properties of block copolymer F127-SS-TOC, RES was encapsulated by the F127-SS-TOC polymer and formed RES-loaded micelles (F127-SS-TOC/RES) in aqueous solution by self-assembly via a solvent evaporation method. The drug loading of F127-SS-TOC/RES micelles was 13.25 ± 2.29%, which remained stable for 7 days at 25 °C. The particle size and zeta potential of the above-mentioned micelles measured by dynamic light scattering (DLS) were 39.50 ± 1.39 nm and −4.55 ± 0.39 mV, respectively. Besides, F127-SS-TOC/RES micelles have significant cytotoxicity in human breast cancer cells MCF-7 and MDA-MB-231 compared to free RES and non-redox-sensitive F127-TOC/RES micelles. The results also showed that redox-sensitive F127-SS-TOC/RES micelles could induce apoptosis and elevate the intracellular reactive oxygen species (ROS) level against MDA-MB-231 cells. Hence, our results indicated that RES loaded F127-SS-TOC micelles hold potential in improving the treatment of breast cancer.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
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DOI
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2017
·Vol. 17
·期 7
·4532-4541
·
IF 1.483
Li Lidong,Shang Le,Chen Kanglong,Wang Qiuyue,Luo Jianbin,Zhou Qinghan,Lin Juan
A novel redox-sensitvie core cross-linked micelles based on disulfide-linked PEG-polypeptide hybrid polymer were prepared and demonstrated for anticancer drug delivery, where N,N-bis(acrylate) cystamine (BAC) served as cross-linker, allyl-terminated poly(γ-benzyl-L-glutamate)
(PBLG) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The molecular structure and characteristics of the cross-linked micelle and the precursor were confirmed by 1H NMR and FT-IR. The cross-linked micelles could be easily degraded into individual linear short
chains (Mn
= 1800) in the presence of 20 mM glutathione (GSH) by the cleavage of the disulfide linkages from the cross-linker BAC. Doxorubicin (DOX) was selected as a model anticancer drug and encapsulated into the micelles with a decent drug loading content of 21.6 wt%.
Compared to the burst release of free DOX in first 6 hours, the in vitro release studies revealed that the micelles exhibited a sustained and high cumulative drug release in GSH (up to 86%) within 24 h, rather than the relatively low release rate of 62% in PBS (pH 7.4). Cell cytoxicity
experiments showed that the obtained micelles exhibited nontoxic, and the drug-loaded micelles exhibited high anti-cancer efficacy. All the results showed that the designed cross-linked PEG-polypeptide hybrid micelles may be a promising vehicle for anticancer drug delivery with stimuli-triggered
drug release behavior in reducing environment.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
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DOI
高影响因子
Drug Delivery and Translational Research
·
2021
·Vol. 12
·期 3
·550-561
·
IF 4.617
Wen Yi,Song Zhimei,Xu Hongmei,Feng Sijia,Zhu Li,Teng Fangfang,Feng Runliang
In the study, new polymeric micelles loaded with azithromycin were prepared to enhance azithromycin’s solubility and evaluate its in vitro/in vivo antibacterial activity against Staphylococcus aureus . Amphiphilic α-Linolenic acid-methoxy poly (ethylene glycol) polymer (MPEG-LNA) was synthesized through DCC-DMAP esterification procedure. Through thin-film hydration method, optimized azithromycin-loaded micelles (AZI-M) were prepared with 87.15% of encapsulation efficiency and 11.07% of drug loading capacity when the ratio of LNA to MPEG was 4. Azithromycin’s water-solubility was obviously enhanced due to its loading into the polymeric micelles. The azithromycin-loaded micelles were characterized in terms of x-ray diffraction, Fourier transform infrared spectroscopy, in vitro release, and in vitro / in vivo antibacterial experiments. Although the drug-loaded micelles provided a slow and continuous azithromycin’s release in comparison with free azithromycin, in vitro antibacterial activity results confirmed that its effect on the inhibition of bacterial growth and biofilm formation was similar to free azithromycin. It is more interesting that the azithromycin-loaded micelles achieved good in vivo antibacterial therapeutic effect like QiXian® (azithromycin lactobionate injection) in mouse model of intraperitoneal infection. AZI-M can be considered as a potential candidate for in vivo antibiotic therapy of Staphylococcus aureus infections. Graphical abstract
研究领域:
药剂学
·
微生物学
·
材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Nan Zhang,Xuefan Xu,Xue Zhang,Ding Qu,Lingjing Xue,Ran Mo,Can Zhang
Development of combination photothermal–chemotherapy platform is of great interest for enhancing antitumor efficacy and inhibiting tumor recurrence , which supports selective and dose-controlled delivery of heat and anticancer drugs to tumor. Here, an injectable nanocomposite hydrogel incorporating PEGylated gold nanorods (GNRs) and paclitaxel-loaded chitosan polymeric micelles (PTX-M) is developed in pursuit of improved local tumor control. After intratumoral injection, both GNRs and PTX-M can be simultaneously delivered and immobilized in the tumor tissue by the thermo-sensitive hydrogel matrix. Exposure to the laser irradiation induces the GNR-mediated photothermal damage confined to the tumor with sparing the surrounding normal tissue. Synergistically, the co-delivered PTX-M shows prolonged tumor retention with the sustained release of anticancer drug to efficiently kill the residual tumor cells that evade the photothermal ablation due to the heterogeneous heating in the tumor region. This combination photothermal–chemotherapy presents superior effects on suppressing the tumor recurrence and prolonging the survival in the Heps-bearing mice, compared to the photothermal therapy alone.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2020
·Vol. 44
·期 29
·12633-12638
·
IF 3.288
Weili Xue,Ashish Trital,Sihang Liu,Liangbo Xu
To simplify the preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu–Lys–Cys–Glu–Lys (EKCEK) were reacted with methacrylohydrazide (MAH) by click reaction, the product was further conjugated with doxorubicin (Dox) to form amphipathic molecules, and finally the amphipathic molecules self-assembled into doxorubicin-loaded micelles (EKCEK–Dox) in deionized water. TEM and DLS results showed that the EKCEK–Dox micelles were of the regular sphere, with the mean diameter approximately 70 nm. The drug-loading capacity of the prepared micelles was up to 44.6%, and the micelles were very stable in PBS solution. In vitro antitumor experiment showed that the EKCEK–Dox micelles had significant inhibition efficacy on MCF-7 cells, which was much better than the clinical antitumor drug (Doxil®). The IC50 of the EKCEK–Dox micelles (5.6 μg Dox equiv. per mL) was significantly lower than Doxil (8.9 μg Dox equiv. per mL). Therefore, the drug delivery system based on zwitterionic oligopeptides will be a promising strategy for cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物材料
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DOI
高影响因子
Polymer Chemistry
·
2014
·Vol. 5
·期 16
·4734-4746
·
IF 5.368
Haiyan Chen,Yuqi Chen,Haibo Yang,Weixia Xu,Min Zhang,Yuxiang Ma,Samuel Achilefu,Yueqing Gu
Conventional chemotherapy suffers from non-specificity, lack of aqueous solubility and multidrug resistance. Tumor-targeting nanotherapeutics exhibit unique advantages in the delivery of drugs specifically into tumors. Here, folic acid (FA), methionine (Met) and a near infrared (NIR) fluorescence probe (cypate, ICG derivative) were all bio-conjugated to succinyl-chitosan (SC) micelles. An anti-cancer drug (paclitaxel, PTX) was loaded into the hydrophobic cores of the formed FA–Met–SC–ICG derivative (FMSCI) micelles, which were under 200 nm in size. In comparison with micelles containing a single targeting moiety (FA or Met), FA and Met co-mediated micelles presented excellent biocompatibility, much higher affinity for cancer cells and excellent tumor-specific distribution in tumor-bearing mice. In vivo anti-tumor activity demonstrated that PTX-loaded FMSCI provided favourable therapeutic efficacy for tumors. In this research, novel nanotherapeutics based on FMSCI loaded with an anti-cancer drug provide a promising nanocomposite for combined tumor-targeting imaging and therapy.
研究领域:
纳米医学
·
癌症治疗学
·
药物递送系统
·
分子成像
·
生物医学工程
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DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2015
·Vol. 132
·期 18
·
IF 1.768
Hongchuan Wu,Zhiguo Li,Libin Zhu,Jiyou Gu
Aqueous polyurethane micelles from 2,4,6-trichlorphenol blocking terminal-isocynate pre-polymer were prepared which could be de-blocked at low temperature. The prepared aqueous blocked polyurethane micelles (BPUMs) were uniform and spherical micro-particles. The particle size was decreased with increase of the DMPA content, while it was enlarged at first and then gradually decreased by increasing R -value. The stability of the micelles was affected by the R value, blocked efficiency and DMPA content. HDI-BPUMs were more stable than HDI-BPUMs at the same condition. The stability was further researched by the zeta potential combining with technique and viscosity tracking method, and the initial zeta potential be used as the stability criterion. In addition, a stabilization mechanism of the micelles was proposed. TCP-blocked TDI-BPUMs could be initially de-blocked at about 75°C and TCP-blocked HDI-BPUMs was de-blocked at about 80°C. The de-blocking temperature could be further reduced in the presence of catalyst, but it was scarcely affected by the change of R -value and DMPA content. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 41908
研究领域:
高分子化学
·
胶体与界面科学
·
材料化学
·
功能材料
·
纳米材料
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DOI
高影响因子
BIOMACROMOLECULES
·
2015
·
IF 5.75
Jingxin Gou,Shuangshuang Feng,Helin Xu,Guihua Fang,Yanhui Chao,Yu Zhang,Hui Xu,Xing Tang
Cargo-loading capacity of polymeric micelles could be improved by reducing the core crystallinity and the improvement in the amount of loaded cargo was cargo-polymer affinity dependent. The effect of medium chain triglyceride (MCT) in inhibiting PCL crystallization was confirmed by DSC and polarized microscope. When incorporating MCT into polymeric micelles, the maximum drug loading of disulfiram (DSF), cabazitaxel (CTX), and TM-2 (a taxane derivative) increased from 2.61 ± 0.100%, 13.5 ± 0.316%, and 20.9 ± 1.57% to 8.34 ± 0.197%, 21.7 ± 0.951%, and 28.0 ± 1.47%, respectively. Moreover, the prepared oil-containing micelles (OCMs) showed well-controlled particle size, good stability, and decreased drug release rate. MCT incorporation showed little influence on the performances of micelles in cell studies or pharmacokinetics. These results indicated that MCT incorporation could be a core construction module applied in the delivery of hydrophobic drugs.
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Hao Tang,Hanbing Wang,Zhihua Gan,Zhenshan Ding,Qingsong Yu
The cationic surface charge critically influences the biological functions and therapeutic outcomes of the cancer nanomedicines. However, the basic correlation between the cationic group categories and their therapeutic efficacy has not been elucidated. In this study, cationic polymeric nanoparticles with amino groups (primary, tertiary, and quaternary amines) as the single variable were leveraged to investigate the various effects of amino species for enhanced antitumor chemotherapy. The nanoparticles were constructed from a series of triblock polymers with varying cationic repeating units at the hydrophilic–hydrophobic interface. Our results suggested that quaternary ammonium outperforms its primary and tertiary counterparts in destroying mitochondrial membranes to induce apoptosis, penetrating deep inside the tumor tissue, and damaging tumor vasculatures. As a result, we were able to effectively inhibit tumor growth in mice by a quaternary ammonium conjugate without causing significant toxicity. Our work demonstrated that the chemical structures played vital roles in regulating their biological functions and provided valuable information for designing cationic drug delivery systems.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
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DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Yunfang Zhou,Shuanghu Wang,Xuhua Ying,Yifan Wang,Peiwu Geng,Aiping Deng,Zhihong Yu
Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy.
研究领域:
药学
·
肿瘤学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Chunpeng Yang,Mengdi Wu,Min Li,Wenbin Niu,Yinan Zhao,Shubiao Zhang
MST and CD quantitatively confirmed that the flexible ADH-DTDPA spacer preserves strong CD44 binding ( K D = 15.3 μM). • HPMs showed pH/redox-triggered release, with 78.2% payload release in 72 h under tumor-mimicking conditions. • HPMs achieved superior antitumor efficacy at a lower dose while reducing systemic toxicity in vivo . Clinical application of podophyllotoxin (PPT) is significantly hampered by poor aqueous solubility and considerable systemic toxicity. Herein, we engineered dual-targeting and dual-cleavable prodrug micelles (HPMs) by conjugating PPT to hyaluronic acid (HA) backbone via a flexible, dual-responsive spacer, adipic dihydrazide–3,3′-dithiodipropionic acid (ADH-DTDPA). In vitro , HPMs demonstrated efficient CD44-mediated internalization in NCI-H1299 cells and rapidly disassembled under tumor microenvironment (TME) conditions (pH 5.0/GSH). Crucially, microscale thermophoresis (MST) provided quantitative evidence of the targeting mechanism, revealing a high binding affinity ( K D = 15.3 μM) for the CD44 receptor. In vivo , this design achieved effective accumulation of the micelles at tumor sites. Notably, HPMs (10 mg/kg) achieved superior tumor inhibition compared to free PPT (15 mg/kg) without inducing hepatotoxicity or nephrotoxicity. These findings provide a safe delivery strategy to overcome the clinical limitations of PPT and offer quantitative molecular insights into the rational design of targeted nanomedicines for lung cancer therapy. Download: Download high-res image (244KB) Download: Download full-size image
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·682
·
IF 6.9
Shiyuan Lin,Feixian Lu,Qiao Li,Kefeng Zhang,Wei Zhang,Hui Chen,Jianxin Wang
Background : Hepatic fibrosis is characterized by the abnormal activation of hepatic stellate cells (HSCs) and excessive deposition of the extracellular matrix. Currently, effective clinical therapeutic strategies remain limited. Modulating ferroptosis-related pathways in activated HSCs has emerged as a promising therapeutic target for hepatic fibrosis treatment. Methods : An amphiphilic copolymer was synthesized by conjugating COS with ART, which spontaneously self-assembled into micelles; subsequent modification with retinoic acid (RA) yielded RA-functionalized ART–COS copolymer micelles. Curcumin was selected as a model drug to evaluate the potential of the micelles in enhancing intestinal epithelial transport, oral absorption and bioavailability. Meanwhile, in vitro targeting ability, capacity to modulate ferroptosis in HSCs and in vivo therapeutic efficacy were systematically investigated. Results : The RA-functionalized ART–COS micelles significantly enhanced intestinal epithelial drug transport, oral absorption, and bioavailability. In vitro experiments demonstrated that the micelles preferentially accumulate in activated HSCs, inhibit GPX4 expression, and induce excessive ROS production and ferroptosis, thereby effectively attenuating hepatic fibrosis. In vivo studies confirmed that the micelles regulated extracellular matrix metabolism, reduced collagen deposition, suppressed the activation and proliferation of HSCs, and ultimately helped attenuate hepatic fibrosis progression. Conclusions : This study successfully developed RA-functionalized ART–COS copolymer micelles. The micelles improve the accumulation of artesunate in liver tissue and yield favorable anti-fibrotic effects, thereby providing a promising translational strategy for anti-fibrotic therapy.
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DOI
PubMed
高影响因子
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