ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Ying Hao,Jinrong Peng,Yaguang Zhang,Lijuan Chen,Feng Luo,Cheng Wang,Zhiyong Qian
Breast cancer has been the first killer among women. In this study, combretastatin A-4 (CA-4) loaded 5-amino acid peptide Ala-Pro-Arg-Pro-Gly (APRPG) modified PEG-PDLLA mixed micelles was developed to target tumor neovasculature for breast cancer therapy. CA-4 is an effective vascular disrupting agent. The APRPG-modified PEG-PDLLA polymer was successfully synthesized and thin-film hydration method was used to prepare APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles. Drug loading capacity (DL), encapsulation efficiency (EE), and the optimized ratio of APRPG-PEG-PDLLA: MPEG-PDLLA for efficient drug loading was investigated. The particle size, zeta potential, morphology, and the crystallographic study were carried out to characterize the micelles. In vitro release study revealed a sustained release of CA-4 from the mixed micelles while compared to free CA-4. Moreover, the cytotoxicity data of blank and drug loaded mixed micelles suggested that the APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles were safe drug carriers and the encapsulated CA-4 remained potent antitumor effect. The cellular uptake study and the in vivo imaging and biodistribution study demonstrated that the APRPG peptide modified mixed micelles has the higher cellular uptake efficiency and could significantly facilitate the accumulation at tumor site. Furthermore, the micelles were slowly extravasated from blood vessels and inhibited embryonic angiogenesis in the transgenic zebrafish model. Consequently, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles group demonstrated a significant inhibition of tumor growth in 4T1 breast cancer model. In short, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles might have great potential for breast cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
高影响因子
LANGMUIR
·
2017
·
IF 3.833
Tingting Zhou,Jiagen Li,Xu Jia,Xubo Zhao,Peng Liu
Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated oxidized alginate (mPEG-OAL) cross-linked with bioreducible disulfide bond. The effect of the complexation with cyclodextrins (α-CD and β-CD) before or after the cross-linking of the mPEG-OAL on the DOX content and controlled release performance was investigated. It was found that the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(CD)-OAL-DOX/Cys, prepared by cross-linking of the mPEG-OAL after complexation with cyclodextrins, exhibited better pH/reduction dual-responsive controlled release performance than the mPEG-OAL-DOX/Cys(CD) ones prepared by cross-linking of the mPEG-OAL before complexation with cyclodextrins, owing to the supramolecular cross-linking of the adjacent pseudopolyrotaxanes. Especially for the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(α-CD)-OAL-DOX/Cys, DOX was released rapidly under lower pH media mimicking the tumor microenvironment and completely released within 48 h, while the premature leakage under the simulated physiological condition was ∼40%, without burst release in both cases. The cellular toxicity and uptake results demonstrated that the mPEG(α-CD)-OAL-DOX/Cys prodrug nanohydrogels possessed similar inhibition against cancer cell growth in comparison with the free DOX and enhanced drug intracellular accumulation.
研究领域:
药剂学
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生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2013
·Vol. 51
·期 9
·2049-2057
·
IF 3.543
Xueqi Qian,Zhengyang Jiang,Xianfu Lin,Qi Wu
Amphiphilic poly(amine-co-ester)s, which contain a single effective enantiomer of an asymmetric drug and thus can avoid potentially serious side effects, are difficult to prepare through nonselective chemical routes not only in the process of introducing chiral drugs to the polymer, but also in the synthesis of the polymer's backbone by metal catalysts. A model of racemic mexiletine, an important antiarrhythmic agent, was used to demonstrate the tandem combination of Candida antarctica lipase B (CAL-B)- and Pd/C-catalyzed dynamic kinetic resolution (DKR) and subsequent CAL-B-catalyzed polycondensation, as an efficient protocol to prepare poly(ethylene glycol)-functionalized poly(amine-co-ester)s containing (R)-mexiletine with 99% ee value. Chemoenzymatic DKR and enzymatic polymerization conditions were optimized, and the optical purity of incorporated (R)-mexiletine was confirmed through its hydrolysis from polyester. The copolymers can readily self-assemble into nanometer-scale-sized micelles with well-dispersed spheres, which have a size distribution that can be efficiently adjusted by changing the polymer concentration. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
研究领域:
生物化学
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制药工程
·
高分子化学
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2019
·Vol. 55
·期 4
·1702-1714
·
IF 3.442
Shao Qi,Feng Yechen,Wang Wenwu,Wang Min,Li Binbin,El Tahchi Mario,Yin Yixia
Chemotherapeutic drugs have shown some limitations in anti-tumor treatment, such as drug resistance, high toxicity and limited regime of clinical uses. Natural products have attracted extensive attention as potential source of unmodified chemical compounds for disease treatment. Withaferin A (WA) has the potential to inhibit multiple human tumors, but it is hardly available for oral administration due to its low water solubility and its side effects. We developed a methoxy poly(ethylene glycol) (mPEG) conjugated poly( d , l -lactide- co -glycolide) (PLGA) drug carrier particles to encapsulate WA for pancreatic cancer treatment. The results showed that WA does not lose its physicochemical properties after encapsulation, and our drug carriers are completely degraded within 1 month. We used the WA-loaded mPEG–PLGA particles for pancreatic cancer cell treatment where it exhibited stronger inhibition than free drug (WA) at the early treatment stage. Our formulation of the drug carriers provides an efficient encapsulation of WA that allows it bonding with heat shock proteins, thereby reducing the expression of AKT and CDK4 proteins to induce apoptosis in cancer cells. Together, our data demonstrate that mPEG–PLGA loaded with WA can achieve the design goals for cancer therapy given its advantages of sustained release and degradation property to reduce the side effect of WA, which provides a possibility for WA to be used in clinical applications.
研究领域:
药学
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肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Polymers
·
2021
·Vol. 13
·期 23
·4096
·
IF 4.329
Lin Wang,Yanqiang Ni,Xin Qi,Liqun Zhang,Dongmei Yue
Hydrogenated Nitrile Rubber (HNBR) is widely used in aerospace, petroleum exploration and other fields because of its excellent performances. However, there remains a challenge of balancing the oil resistance and the low temperature resistance for HNBR. In this work, a series of grafted carboxyl nitrile rubber (XNBR) was prepared by the esterification reaction between active functional groups (–COOH) of XNBR and alkanols of different molecular chain lengths (C8H17OH, C12H25OH, C16H33OH, C18H37OH) or Methoxypolyethylene glycols (MPEG) of different molecular weights (Mn = 350, 750, 1000). The structure and low temperature resistance of as-obtained grafted polymers were characterized by Fourier Transform Infrared (FTIR),1H-NMR and Differential scanning calorimetry (DSC). It was found that the glass transition temperatures (Tg) of grafted XNBR were significantly decreased. MPEG grafted polymers with better low temperature resistance were then selected for hydrogenation. As-prepared hydrogenated XNBR grafted with MPEG-1000 (HXNBR-g-1000) showed the lowest Tgof −29.8 °C and the best low temperature resistance. This work provides a novel and simple preparation method for low temperature resistant HNBR, which might be used potentially in extremely cold environments.Keywords:hydrogenated nitrile rubber (HNBR);grafting;low temperature resistance
研究领域:
材料科学
·
高分子化学
·
航空航天工程
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Shuqin Chen,Miaowei Jiang,Hangbiao Wei,Fangkun Yang,Kai Wang,Li Li,Jinhui Shang
Copper ions (Cu 2+ ) play a critical role in physiological and pathological processes, including diabetes. However, detecting Cu 2+ with high sensitivity and specificity in diabetes remains challenging. In this study, we developed a hemicyanine-based copper ion probe (CUP) encapsulated in mPEG-DSPE nanoparticles (CUNP) for dual-modality fluorescence and photoacoustic (PA) imaging of Cu 2+ . CUNP exhibited excellent aqueous solubility, biocompatibility, and a turn-on response to Cu 2+ , with activate signals. In vivo studies in streptozotocin (STZ)-induced diabetic mice revealed elevated hepatic Cu 2+ levels, which were attenuated by metformin treatment, as confirmed by PA and fluorescence imaging. Urine analysis further revealed elevated Cu 2+ in diabetic patients. These findings highlight CUNP as a promising tool for non-invasive Cu 2+ monitoring in diabetes, with potential clinical applications in disease diagnosis and therapeutic evaluation.
研究领域:
生物医学工程
·
分子影像学
·
代谢疾病研究
·
纳米医学
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转化医学
·
生物分析化学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2020
·
IF 4.032
Yang Li,Yu Liu,Hongyu Zhu,Shirong Shuai,Cong Zhao,Kanghong Zhou,Wei Ge,Jianyuan Hao
Methoxy-poly (ethylene glycol)-block-poly (α-carboxyl-ε-caprolactone)/Fe 3 O 4 nanocomposites (mPEG-b-PCCL@Fe 3 O 4 ) with spherical shape, more negative and smoother surface and core-sell structure were prepared by simply changing the solvent. Their degradation behavior was systematically investigated at 37 °C in distilled water and buffers with different pH values. The mPEG-b-PCCL micelles were used as the contrast. Although the acid inhibition and basic promoting degradation were observed for both mPEG-b-PCCL@Fe 3 O 4 and micelles, the existence of magnetite nanoparticles (MNPs) and more surface –COOH slowed down the degradation of nanocomposites due to the dissociation hindrance of –COOH, the hydrophobicity and the cross-linking effects of MNPs. The degradation of mPEG-b-PCCL@Fe 3 O 4 underwent the surface degradation at initial time and bulk degradation after complete swelling of the hydrophobic core. These investigations suggested that the degradation of mPEG-b-PCCL@Fe 3 O 4 was more designable and controllable than that of micelles.
研究领域:
材料科学
·
纳米技术
·
聚合物化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2013
·Vol. 31
·期 2
·291-304
·
IF 4.742
Yang Xiao-Li,Luo Yan-Ling,Xu Feng,Chen Ya-Shao
Purpose Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. Methods The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV–vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. Results The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96–27.64 mg L −1 . The micelles were narrow-size-distribution, with hydrodynamic diameters about 128–193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. Conclusions The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.
研究领域:
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
·
2016
·Vol. 38
·期 7
·1121-1129
·
IF 1.639
Zhou Jian Qin,He Ting,Wang Jian Wen
Objectives To establish a method for microbial trans glutaminase (mTG)-mediated PEGylation of proteins at the level of lysine (Lys) residues. Results Carboxybenzyl-glutaminyl–glycinyl-methoxypolyethylene glycol (CBZ-QG-mPEG) was prepared by introducing carboxybenzyl-glutaminyl-glycine (CBZ-QG) to mPEG amine. The analysis by Fourier transform infrared spectroscopy and SDS-PAGE showed that CBZ-QG-mPEG was successfully synthesized and can be recognized by mTG as an acyl donor to modify therapeutic protein, cytochrome c (cyt c ). Finally, under an optimized condition (cyt c 0.5 mg/ml, CBZ-QG-mPEG 11.25 mg/ml, mTG 0.5 mg/ml, 37 °C, 2 h), the PEGylation yield reached 76.5 %. Conclusions This is the first study regarding the PEGylation of protein at the level of Lys residues catalyzed by mTG. The novel method could be employed to immobilize active proteins and modify therapeutic proteins.
研究领域:
生物化学
·
蛋白质工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 68
·63597-63606
·
IF 3.289
Shasha Zhao,Xiaoshan Fan,Xiaoyan Li,Xianglin Lv,Weiwei Zhang,Zhiguo Hu
Y-Shaped amphiphilic copolymers (zwitterionic-(PLLA2.5K)2 and MPEG-(PDLA2.5K)2) were simply synthesized through click reaction of alkyne-(PLA2.5K)2 and zwittterionic-N3 or MPEG-N3. Gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (1H NMR) were employed to characterize the composition and structure of these copolymers. The stereocomplexes were prepared from pairs zwitterionic-(PLLA2.5K)2/MPEG-(PDLA2.5K)2 (molar ratio = 1 : 1), and confirmed by differential scanning calorimeter (DSC). Furthermore the aggregation behaviors for these synthesized polymers and their stereocomplexes had been proved by fluorescence spectroscopy (PL), transmission electron microscopy (TEM), dynamic light scattering (DLS) and static light scattering (SLS), and zeta potential. Their critical micelle concentration (CMC) obtained by PL was 0.0213 mg mL−1 for zwitterionic-(PLLA2.5K)2/MPEG1.9K-(PDLA2.5K)2 and 0.1265 mg mL−1 for zwitterionic-(PLLA2.5K)2/MPEG5K-(PDLA2.5K)2. The stereocomplexes could self-assemble into spherical micelles with diameters of 76 nm (zwitterionic-(PLLA2.5K)2/MPEG1.9K-(PDLA2.5K)2) and 89 nm (zwitterionic-(PLLA2.5K)2/MPEG5K-(PDLA2.5K)2) respectively. The biocompatibility of these copolymers and their stereocomplexes was evaluated with relatively low cytotoxicity. The DOX-loaded micelles of the stereocomplexes had a higher drug loading content and encapsulation efficiency, and could release DOX in a controlled manner. Therefore, the new stereocomplex zwitterionic-(PLLA)2/MPEG-(PDLA)2 has great potential as a hydrophobic drug nanocarrier.
研究领域:
生物材料
·
药物递送系统
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2015
·
IF 4.383
Tianpeng Zhang,Huan Wang,Yanghuan Ye,Xingwang Zhang,Baojian Wu
Polymeric micelles receive considerable attention as drug delivery vehicles, depending on the versatility in drug solubilization and targeting therapy. However, their use invariably suffers with poor stability both in in vitro and in vivo conditions. Here, we aimed to develop a novel nanocarrier (micellar emulsions, MEs) for a systemic delivery of genistein (Gen), a poorly soluble anticancer agent. Gen-loaded MEs (Gen-MEs) were prepared from methoxy poly(ethylene glycol)-block-(ε-caprolactone) and medium-chain triglycerides (MCT) by solvent-diffusion technique. Nanocarriers were characterized by dynamic light scattering, transmission electron microscopy, and in vitro release. The resulting Gen-MEs were approximately 46 nm in particle size with a narrow distribution. Gen-MEs produced a different in vitro release profile from the counterpart of Gen-ME. The incorporation of MCT significantly enhanced the stability of nanoparticles against dilution with simulated body fluid. Pharmacokinetic study revealed that MEs could notably extend the mean retention time of Gen, 1.57- and 7.38-fold as long as that of micelles and solution formulation, respectively, following intravenous injection. Furthermore, MEs markedly increased the elimination half-life (t1/2β) of Gen, which was 2.63-fold larger than that of Gen solution. Interestingly, Gen distribution in the liver and kidney for MEs group was significantly low relative to the micelle group in the first 2 hours, indicating less perfusion in such two tissues, which well accorded with the elongated mean retention time. Our findings suggested that MEs may be promising carriers as an alternative of micelles to systemically deliver poorly soluble drugs.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Shiya Zhou,Wei Sun,Yinglei Zhai
Currently, nanoparticles (NPs) made of amphiphilic block copolymer are still an essential part of drug delivery system. Here, we report a novel amphiphilic block copolymer and paclitaxel (PTX)-loaded copolymer NPs for the controlled delivery of PTX. The block copolymer was synthesized via melt polycondensation method of methoxy poly(ethylene glycol) (mPEG), sebacic acid (SA) and ricinoleic acid (RA). A series of characterization approaches such as Fourier Transform Infrared Spectroscopy (FTIR), 1Hydrogen-Nuclear Magnetic Resonance (1H-NMR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Gel Permeation Chromatography (GPC) applied have shown that the amphiphilic block copolymer was prepared as designed. NPs prepared by nanoprecipitation method consist of mPEG segments as the hydrophilic shell and RA-SA segments as the hydrophobic core, hydrophobic PTX was encapsulated as model drug. Subsequently, Transmission Electron Microscopy (TEM) analysis indicated that the spherical NPs have effective mean diameters ranging from 100 to 400 nm. Dynamic Light Scattering (DLS) analysis also revealed the controllable NPs diameter by modulating the mass ratio of RA to SA and drug loading amount (DLA). Besides, biphasic profile with zero order drug release was observed in general in vitro release behaviors of PTX from NPs. Further investigation confirmed that the release behaviors depend on the crystallinity of hydrophobic RA-SA segments. Results above suggest that NPs with amphiphlic block copolymer mPEG-b-P(RA-SA)-b-mPEG have a remarkable potential as a carrier for hydrophobic drug delivery in cancer therapy.
研究领域:
药剂学
·
材料科学
·
肿瘤学
✓ 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）