Materials
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2015
·Vol. 8
·期 2
·379-391
·
IF 2.651
Yanchao Liang,Zhihui Su,Yao Yao,Na Zhang
A novel polymer-drug conjugate was prepared by the chemical reaction between the copolymer Pluronic P123 and the docetaxel via a pH sensitive hydrazone bond. These pluronic P123-docetaxel (DTX) conjugates (P123-DTX) could form the stable drug-loaded materials that can self-assemble into the defined nano-micelles in aqueous solution because of their obvious amphiphilic property and low critical micelle concentration. The spherical morphology and particle size of the prepared nano-micelles were characterized by transmission electron microscopy and dynamic light scattering, respectively. Moreover, after the introduction of pH sensitive hydrazone bond, P123-DTX micelle showed a pH dependent drug release behavior. At pH 5.0 (in 48 h), the cumulative release amount of DTX were ~84.9%, which is about six times higher than that at pH 7.4. The prepared novel p123-DTX conjugates may offer a great benefit for drug delivery and controlling the drug release.Keywords:docetaxel;conjugates;nano-micelles;stability;pH controlled release
研究领域:
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Ke Du,Xiao Li,Fude Feng
Polymer–drug conjugates (PDCs) provide possibilities for the development of multiresponsive drug delivery and release platforms utilized in cancer therapy. The delivery of Temozolomide (TMZ, a DNA methylation agent) by PDCs has been developed to improve TMZ stability under physiological conditions for the treatment of glioblastoma multiforme (GBM); however, with inefficient chemotherapeutic efficacy. In this work, we synthesized an amphiphilic triblock copolymer (P1-SNO) with four pendant functionalities, including (1) a TMZ intermediate (named MTIC) as a prodrug moiety, (2) a disulfide bond as a redox-responsive trigger to cage MTIC, (3) S-nitrosothiol as a light/heat-responsive donor of nitric oxide (NO), and (4) a poly(ethylene glycol) chain to enable self-assembly in aqueous media. P1-SNO was demonstrated to liberate MTIC in the presence of reduced glutathione and release gaseous NO upon exposure to light or heat. The in vitro results revealed a synergistic effect of released MTIC and NO on both TMZ-sensitive and TMZ-resistant GBM cells. The environment-responsive PDC system for codelivery of MTIC and NO is promising to overcome the efficacy issue in TMZ-based cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2018
·Vol. 40
·期 2
·289-295
·
IF 2.569
Chunye Liu,Xuejiao Zhang,Hui Jing,Jingshui Zhang,Yanqing Miao,Xifeng Zhai,Songyi Chen
An open-tubular capillary electrochromatography method has been developed for the determination of binding constants between β 2 -adrenergic receptor ( β 2 -AR) and seven drugs . β 2 -AR was oriented immobilized onto one part of inner surface of capillary via microwave-assisted technical synthesis. According to the linear relationship between coating length and the apparent mobility of analyte, the binding constant ( K b ) can be obtained by related theories and equations. The order of K b values between drugs such as adrenaline hydrochloride, norepinephrine bitartrate, and propranolol hydrochloride with β 2 -AR is well consistent with that reported in the literature. By the method, K b values between four extracts of Radix Paeoniae Rubra and β 2 - AR were also successfully obtained. Subsequently, computer models were applied to interpret the CEC experiments. And the results proved to be in good agreement with the method. The work, herein, demonstrates the potential of the method in drug-receptor affinity interactions evaluation and screening of lead compounds from natural sources.
研究领域:
药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2012
·Vol. 2
·期 1
·1-8
·
IF 0
Wang Bing,Yuan Huanxiang,Zhu Chunlei,Yang Qiong,Lv Fengting,Liu Libing,Wang Shu
For most molecule-targeted anticancer systems, intracellular protein targets are very difficult to be accessed by antibodies and also most efforts are made to inhibit protein activity temporarily rather than inactivate them permanently. In this work we firstly designed and synthesized multifunctional polymer-drug conjugates (polythiophene-tamoxifen) for intracellular molecule-targeted binding and inactivation of protein (estrogen receptor α, ERα) for growth inhibition of MCF-7 cancer cells. Small molecule drug was conjugated to polymer side chain for intracellular signal protein targeting and simultaneously the fluorescent characteristic of polymer for tracing the cellular uptake and localization of polythiophene-drug conjugates by cell imaging. Under light irradiation, the conjugated polymer can sensitize oxygen to produce reactive oxygen species (ROS) that specifically inactivate the targeted protein and thus inhibit the growth of tumor cells. The conjugates showed selective growth inhibition of ERα positive cancer cells, which exhibits low side effect for our intracellular molecule-targeted therapy system.
研究领域:
药理学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
Acta Biomaterialia
·
2016
·
IF 6.008
Zhoujiang Chen,Nan He,Maohua Chen,Long Zhao,Xiaohong Li
Micelles self-assembled from drug-conjugated polymers indicate advantages in alleviating the premature release before reaching the intended site. Hyaluronic acid (HA) is known to specifically bind with a transmembrane glycoprotein CD44 , overexpressed in many types of cancerous cells, and can also be served as micelle carriers. However, an excess amount of drug conjugation to HA backbone may be detrimental to the receptor-mediated cellular uptake. Up to now, the effect of conjugation densities of drugs has never been determined on the physical properties and biological performance of resulting micelles. In the current study, camptothecin (CPT) was conjugated on HA through 3,3′-dithiodipropionic acid to self-assemble into reduction-sensitive micelles. The substitution degrees of CPT on HA backbone were tuned from around 4–20%, to clarify the effects on the cellular uptake efficiency and cytotoxicities of micelles, as well as the tumor accumulation and antitumor efficacy. The CPT substitution degree of around 15% on HA resulted in micelles with a higher cytotoxicity to 4T1 cells and achieved a better balance between the cellular uptake and reduction-triggered drug release, compared with other micelles. In contrast to a fast kidney clearance and an even distribution in major organs after intravenous injection of free CPT, the optimized micelles were accumulated in tumors, livers and lungs. The micelle content indicated a significant decrease in livers after 24 h, while that in tumors displayed a significant increase to 4.9% of the injection dose. The tumor accumulation of micelles led to strong tumor suppression with minimal systemic toxicity. The in situ tumor inhibition and the accumulation of micelles in liver and lungs inhibited tumor metastasis to these tissues. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release. Statement of Significance Hyaluronic acid (HA) can be served as micelle carriers and targeting ligands to tumor cells. However, the effects of drug conjugation densities on the physical profile and biological performance of resulting micelles have never been investigated. In the current study, camptothecin is conjugated on HA with reduction-sensitive linkers, and the substitution degrees of camptothecin on HA backbone vary from around 4–20%. The micelles with a substitution degree of around 15% achieve a better balance between the cellular uptake and reduction-triggered drug release and a higher cytotoxicity than others. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release.
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
PubMed
高影响因子
危险品化学品经营许可证（带存储）