CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Yimu Li,Xuling Chen,Jianbo Ji,Lingbing Li,Guangxi Zhai
In this paper, a novel redox-responsive nanoparticles has been designed for targeted delivery of docetaxel (DTX). Chondroitin sulfate (CS) was used to construct the nanoparticles due to the ability of tumor targeting through binding with CD44 receptor that overexpresses on the surfaces of various tumor cells. A redox-responsive small-molecular DTX prodrug was prepared through modifying with cystamine containing disulfide bonds (Cys-DTX). Then the DTX prodrug was grafted to the CS to construct the amphiphilic polymer (CS-ss-DTX). Further, Cys-DTX/CS-ss-DTX nanoparticles were formed by self-assembly of amphiphilic polymer and incorporation of free Cys-DTX prodrug. This category of nanosized DTX delivery system was expected for not only exhibiting high permeability and cytotoxicity of Cys-DTX prodrug, but also targeting transportation of encapsulated redox-responsive Cys-DTX prodrug. According to results of related researches on physicochemical properties and biological evaluation, the novel redox-responsive Cys-DTX/CS-ss-DTX nanoparticles increased amount of DTX released from the nanoparticles in reductive environment, improved permeability in tumor tissues, enhanced cytotoxicity and decreased side effects compared with free DTX. All of these results showed that this kind of Cys-DTX/CS-ss-DTX nanoparticles were worthy of being expectation in tumor chemotherapy in future.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2016
·Vol. 11
·期 1
·1-9
·
IF 2.584
Xie Yanyan,Zhao Jun,Huang Renliang,Qi Wei,Wang Yuefei,Su Rongxin,He Zhimin
We report a new approach to constructing a peptide–polysaccharide hybrid hydrogel via the calcium-ion-triggered co-assembly of fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) peptide and alginate. Calcium ions triggered the self-assembly of Fmoc-FF peptide into nanofibers with diameter of about 30 nm. Meanwhile, alginate was rapidly crosslinked by the calcium ions, leading to the formation of stable hybrid hydrogel beads. Compared to alginate or Fmoc-FF hydrogel alone, the hybrid Fmoc-FF/alginate hydrogel had much better stability in both water and a phosphate-buffered solution (PBS), probably because of the synergistic effect of noncovalent and ionic interactions. Furthermore, docetaxel was chosen as a drug model, and it was encapsulated by hydrogel beads to study the in vitro release behavior. The sustained and controlled docetaxel release was obtained by varying the concentration ratio between Fmoc-FF peptide and alginate.
研究领域:
生物材料学
·
药剂学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 3
·e14511
·
IF 3.2
Yongpeng Shen,Yilin Cheng,Haotian Hu,Yufeng Liu,Yujie Li,Tianyu Zhu,Defeng Xu,Hang Hu
Docetaxel (DTX) is a semi-synthetic analogue of paclitaxel which has attracted extensive attention in the treatment of cancer. However, the current clinically used DTX formulations display low tumor targeting ability, leading to unsatisfactory therapeutic outcomes with adverse effects, which poses significant challenges to the clinical application. In this study, three galactosamine (Gal) and docetaxel conjugates with different linkers were synthesized, namely DTX-(suc-Gal) 2 , DTX-(DTDPA-Gal) 2 , and DTX-(DSeDPA-Gal) 2 . These three conjugates were characterized by 1 H NMR, FT-IR and HRMS. The in vitro drug release study shows that DTX-(DTDPA-Gal) 2 and DTX-(DSeDPA-Gal) 2 exhibit glutathione (GSH)-responsive drug release and DTX-(DSeDPA-Gal) 2 displays higher GSH-responsiveness. The in vitro antitumor activity study shows that DTX-(DTDPA-Gal) 2 and DTX-(DSeDPA-Gal) 2 exhibit enhanced cytotoxicity, cell apoptosis rate and G2/M phase arrest against HepG2 cells as compared to DTX-(suc-Gal) 2 , DTX-(DSeDPA-Gal) 2 displays the highest cytotoxicity, cell apoptosis rate and G2/M phase arrest among these three conjugates. In addition, DTX-(DSeDPA-Gal) 2 exhibits higher selectivity to HepG2 cells as compared to free DTX. The DTX-(DSeDPA-Gal) 2 developed in this study has been proven to be an effective DTX conjugate for selective killing hepatoma cells.
研究领域:
药理学
·
肿瘤学
·
化学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2013
·Vol. 4
·期 8
·2489-2495
·
IF 5.231
Yajuan Sun,Weibing Dong,Huiyuan Wang,Yongzhuo Huang,Huike Gu,Victor C. Yang,Junbo Gong
Nanorods are capable of enhanced intracellular delivery and prolonged blood circulation over their spherical counterparts, and thus can be used as unmatched drug carriers for cancer chemotherapy. An innovative method was developed to synthesize size-tunable, PMAA@chitosan-based, hollow polymeric nanorods for intracellular delivery, by using mesoporous silica nanorod templates. The morphology of the polymeric hollow nanorods was examined by TEM and FT-IR spectra, which indicated a homogeneous three-dimensional structure. An uptake study using human lung carcinoma A-549 cell lines revealed highly efficient cell internalization of the FITC-labeled nanorods, suggesting the potential of utilizing these nanorods as carriers in achieving effective intracellular drug delivery. Cell viability studies of the docetaxel-loaded nanorods yielded consistent results, as the drug-loaded nanorods produced a significantly higher inhibition of the growth of A-549 tumor cells when compared with treatment by free docetaxel. Overall, this preliminary in vitro investigation sheds light on the use of prepared hollow polymeric nanorods for drug delivery applications.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Hongchen Hua,Xuemei Zhang,Hongjie Mu,Qingqing Meng,Ying Jiang,Yiyun Wang,Xiaoyan Lu,Aiping Wang,Sha Liu,Yaping Zhang,Zhihui Wan,Kaoxiang Sun
Gliomas are the most common malignant brain tumor, but treatment is limited by the blood–brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-( d , l -lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method. The NPs were approximately 110 nm and had smooth surfaces. Enzyme-linked immunoassay results showed that the amount of receptor on the surface of glioma cells was 2.04-fold higher than that of nonmalignant cells, which may promote accumulation of RVG29-modified NPs at the targeting site. NPs showed targeting properties for glioma cells compared with the non-targeting NPs in an in vitro cellular uptake test. Targeted NPs also showed better BBB penetration in an in vitro model. In vivo tests indicated that RVG29-PEG-PLGA-NPs could selectively accumulate in intracranial glioma tissue. In conclusion, these results indicated that the RVG29-modified NPs have potential efficacy for glioma therapy.
研究领域:
药学
·
神经肿瘤学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Zejun Xu,Yi Zhang,Qian Hu,Qiao Tang,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
The development of biocompatible vector for hydrophobic drug delivery remains a longstanding issue in cancer therapy. We design and synthesis a drug delivery system based on HPG modified β -CD ( β -CD-HPG) by conjugating HPG branches onto β -CD core and its structure was confirmed by NMR, FTIR, GPC and solubility. In vitro biocompatibility tests showed that HPG modification significantly improved red blood cells morphology alteration and hemolysis cause by β -CD and β -CD-HPG displayed cell safety apparently in a wide range of 0.01–1 mg/mL. An anti-cancer drug, docetaxel, was effectively encapsulated into β -CD-HPG which was confirmed by DSC analysis. This copolymer could form nanoparticles with small size (< 200 nm) and exhibited better DTX loading capacity and controlled release kinetics without initial burst release behavior compared with β -CD. Furthermore, antitumor assay in vitro show that β -CD-HPG/DTX effectively inhibited proliferation of human breast adenocarcinoma cells. Therefore, β -CD-HPG/DTX exhibit great potential for cancer chemotherapy.
研究领域:
药学
·
生物材料
·
肿瘤学
✓ 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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Leilei Gao,Fang Wang,Tingting Hou,Yanjun Chen,Fang Li,Guanglin Wang,Bangxing Han,Dong Liu
Docetaxel (DTX) is an important broad-spectrum antitumor drug , but poor water solubility and multidrug resistance often limit clinical application. A nitric oxide (NO) donor docetaxel prodrug (DISMN-DTX) was designed and synthesized, through a two-step procedure starting from isosorbide mononitrate . The novel amphiphilic small molecule prodrug is readily self-assembled into nanoplatforms, which effectively solves the significant obstacle of poor water solubility of DTX. Specifically, the DISMN-DTX nanoplatforms could trigger NO release at the intracellular reduction conditions to improve the chemosensitivity of DTX. Thus, our rationally designed prodrug nanoplatforms provide an efficient treatment option for drug-resistant tumors.
研究领域:
药学
·
纳米技术
·
肿瘤学
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产品关联
DOI
高影响因子
NANOTECHNOLOGY
·
2009
·Vol. 20
·期 32
·325102
·
IF 3.446
Jian Zhang,Zhiyu Qian,Yueqing Gu
Thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPA-co-AAm)) nanohydrogel (NHG) with a
diameter of about 50 nm and a lower critical solution temperature (LCST) of about
40 °C
was synthesized by a previously reported precipitation polymerization method. The
physical properties including LCST, diameter and morphology were characterized. Four
hydrophobic model drugs (5-fluorouracil (5-FU), fluorescein, docetaxel (DTX) and
near-infrared dye-12 (NIRD-12)) with different hydrophilicities were respectively entrapped
into the nanoparticles and their in vitro release kinetics from NHG was investigated. DTX
was ultimately chosen as the goal anti-tumor drug and optimally entrapped into NHG with
a drug loading content (DLC) of 7.38% and encapsulation efficiency (EE) of 73.8%. An
in vitro drug release test indicated that DTX-loaded NHG had zero-order release kinetics at
43 °C. The respective anti-tumor efficacy of DTX-loaded NHG with or without hyperthermia on
tumor tissue was evaluated in Kunming mice-bearing S180 sarcoma. The inhibition rates of
DTX-loaded NHG with or without hyperthermia were 78.15% and 48.78%, respectively.
DTX-loaded NHG also showed much lower toxicity during the therapeutic procedure.
Results indicated that this kind of thermally responsive, drug-loaded NHG could be used as
a promising strategy for tumor therapy with the help of local hyperthermia treatment.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2026
·
IF 3.9
Li Qingqing,Liu Yufeng,Zhu Tianyu,Xu Defeng,Hu Hang
Breast cancer stands as the most prevalent type of cancer globally and the leading cause of cancer-related deaths among women. Owing to the substantial side effects associated with conventional treatments such as chemotherapy and radiotherapy, drug delivery systems have been proposed to co-deliver drugs with varying physicochemical properties to tumor cells, thereby achieving a synergistic therapeutic effect. Herein, we designed novel liposomes by membrane hydration method to co-deliver crocetin (CRO) and the chemotherapeutic drug docetaxel (DTX) for the treatment of breast cancer in order to potentiate the efficacy of chemotherapy. The prepared DTX-CRO liposomes (DTX-CRO-Lip) were characterized by transmission electron microscopy (TEM) and dynamic light scattering analysis. DTX-CRO-Lip showed homogeneous spherical morphology and the mean particle size of 75.35 ± 0.52 nm, polydispersity index of 0.26 ± 0.01, and zeta potential of -0.16 ± 0.19 mV. The in vitro drug release study and MTT assays showed that DTX-CRO-Lip had sustained drug release effects and synergistic antitumor effect. The in vivo antitumor efficacy was verified on 4T1 tumor-bearing mice. DTX-CRO-Lip showed the best antitumor efficacy and no apparent side effects, suggesting that it is a promising drug delivery system for the synergistic treatment of breast cancer.
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产品关联
DOI
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 15
·4481
·
IF 4.412
Meng Cheng,Qiaoming Liu,Tiantian Gan,Yuanying Fang,Pengfei Yue,Yongbing Sun,Yi Jin,Jianfang Feng,Liangxing Tu
Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.Keywords:nanocrystals;micelles;circulation;in vivo;docetaxel
研究领域:
药剂学
·
生物医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Enhui Zhang,Ronge Xing,Song Liu,Kecheng Li,Yukun Qin,Huahua Yu,Pengcheng Li
In this study, three different carboxymethyl chitosans (CMCs), namely O-carboxymethyl chitosan (OC), N-carboxymethyl chitosan (NC) and N,O-carboxymethyl chitosan (NOC), were prepared as nano-carriers for an anti-tumor drug, docetaxel (DCT). Three CMCs were fabricated into drug-loading nanoparticles under different preparing conditions respectively. A series of characterization parameters were determined including drug loading capacity (DC), entrapment efficiency (EE), particle size distribution, zeta potential, and morphology, which were used to find the optimized preparing condition for three kinds of nanoparticles (NPs). Furthermore, the in vitro drug release profiles of all the three kinds of nanoparticles showed a sustained release behavior and the release rate of OC-NPs was the fastest. Moreover, compared with NC-NPs and NOC-NPs, OC-NPs exhibited more cellular accumulation in the human gastric carcinoma cells (SGC 7901) as quantitatively determined by the flow cytometry and also much stronger cytotoxicity against these cells. Accordingly, our results showed that drug-loaded nanoparticles formed by different CMCs have dissimilar physiochemical characteristics which subsequently influence their therapeutic effects. We suggest that OC-based nanoparticle is a more desirable anti-tumor drug delivery system than NC-NP and NOC-NP.
研究领域:
药剂学
·
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）