Biomaterials Science
·
2022
·Vol. 10
·期 13
·3454-3465
·
IF 7.59
Peng Dong,Jiaojiao Liu,Hongshuai Lv,Jiaan Wu,Naining Zhang,Si Wang,Xiaohai Li,Jinghua Hu,Anny Wang,Daisy J. Li,Dandan Wang,Shengnan Cao,Liangyu Xie,Yikang Shi
Docetaxel (DTX) has been widely used for the treatment of many types of cancer. However, DTX is poorly water-soluble and commercial DTX is formulated in non-ionic surfactant polysorbate 80 and ethanol, thereby leading to hypersensitivity and serious side effects. Herein, a polymer dual drug conjugate was synthesized by coupling DTX and docosahexaenoic acid (DHA) with bifunctionalized dextran. The polysaccharide conjugate dextran–DHA–DTX possessed high water solubility and was self-assembled into nanoparticles with a diameter of 98.0 ± 6.4 nm. Pharmacokinetic and biodistribution studies showed that the dextran–DHA–DTX dual drug conjugate not only had significantly prolonged blood circulation but was also selectively accumulated in the tumor with reduced drug distribution in normal tissues. The conjugate exhibited a superior therapeutic effect in both xenograft nude mice models without causing any systemic side effects. Notably, the conjugate nearly eliminated all xenograft tumors in nude mice bearing breast cancer cells MCF-7. This study revealed that the dextran-based dual drug delivery system may provide an effective strategy to selectively deliver DTX to tumor sites.
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
Drug Delivery and Translational Research
·
2022
·Vol. 13
·期 4
·983-993
·
IF 5.671
Tong Le,Zhou ZeYang,Wang Gang,Wu Chao
Oral absorption of docetaxel was limited by drug efflux pump p-glycoprotein (P-gp) and cytochrome P450 enzyme (CYP 450). Therefore, co-loading agent that inhibits P-gp and CYP450 in self-nanoemulsifying drug delivery systems (SMEs) is considered a promising strategy for oral delivery of docetaxel. In this study, curcumin was selected as an inhibitor of P-gp and CYP450, and it was co-encapsuled in SMEs to improve the oral bioavailability of docetaxel. SMEs quickly dispersed in water within 20 s, and the droplet size was 32.23 ± 2.21 nm. The release rate of curcumin from DC-SMEs was higher than that of docetaxel in vitro. Compared with free docetaxel, SMEs significantly increased the permeability of docetaxel by 4.6 times. And competitive experiments showed that the increased permeability was the result of inhibition of p-gp. The half-life and oral bioavailabilty of DC-SMEs increased about 1.7 times and 1.6 times than docetaxel SMEs, which indicated that its good pharmacokinetic behavior was related to the restriction of hepatic first-pass metabolism. In conclusion, DC-SME was an ideal platform to facilitate oral delivery of docetaxel through inhibited P-gp and CYP 450. Graphical Abstract
研究领域:
药剂学
·
药理学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Huiyuan Zhang,Kaiming Wang,Pei Zhang,Wenxiu He,Aixin Song,Yuxia Luan
Docetaxel (DTX) can produce anti-tumor effects by inhibiting cell growth and inducing apoptosis. However, the poor solubility of DTX restricts its application and its clinical formulation has caused serious adverse reaction due to the use of Tween-80. In the present study, DTX was conjugated to an amphiphilic di-block polymer to solve these problems. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was selected as the polymer skeleton and a redox sensitive disulfide bond was used as the linker between DTX and mPEG-PCL. The synthesized mPEG-PCL-SS-DTX conjugates were characterized by 1 H-nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FTIR). Interestingly, the mPEG-PCL-SS-DTX conjugates could self-assemble into micelles in aqueous solution. The critical micelle concentration (CMC) of mPEG-PCL-SS-DTX micelles was about 2.3 mg L −1 determined using pyrene molecule fluorescent probe method while the size of mPEG-PCL-SS-DTX micelles was determined to be ca . 17.6 nm and 116.0 nm with a bimodal distribution by dynamic light scattering (DLS). The in vitro release results indicated that the as-prepared micelles exhibited a sustained release profile with good redox sensitive properties. In particular, the hemolytic toxicity test indicated the as-prepared mPEG-PCL-SS-DTX micelles had negligible hemolytic activity, demonstrating their safety in drug delivery system. Cytotoxicity assay of the mPEG-PCL-SS-DTX micelles verified their highly enhanced cytotoxicity to MCF-7/A and A549 cells. These results thus demonstrated that the present redox-sensitive mPEG-PCL-SS-DTX micelle was an efficient and safe sustained drug delivery system in the biomedical area.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2015
·Vol. 16
·期 3
·420-431
·
IF 3.851
Yuanyuan Guo,Pei Zhang,Qingyun Zhao,Kaiming Wang,Yuxia Luan
In this article, the low-molecular weight biodegradable methoxy poly (ethylene glycol)-poly ( d , l -lactide-co-glycolide) (PP) is chosen as polymeric skeleton to be conjugated with docetaxel (DTX) by disulfide bond (PP-SS-DTX) to construct the reduction-sensitive drug delivery system. The conjugates are synthesized via three steps and are further employed to physically load free DTX to develop the PP-SS-DTX/DTX micelles which exhibit many merits including high drug loading content, good stability, and stimuli-sensitive release of drugs. The hydrodynamic diameter of PP-SS-DTX/DTX micelles determined by DLS is 112.3 nm. The hemolysis assay reveals the good blood compatibility of PP-SS-DTX/DTX micelles. In order to investigate the reductive sensitivity of PP-SS-DTX/DTX micelles, dithiothreitol (DTT) is added into the release medium and a programmed drug release mode is observed in the conjugated micelles. In vitro cytotoxity assay shows that the PP-SS-DTX/DTX micelles are more cytotoxic than that of free DTX solution for both MCF-7 and B16F10 cancer cells. In addition, the PP-SS-DTX/DTX micelles also show a higher cellular uptake rate than that of free DTX. Hence, the prepared reduction-sensitive PP-SS-DTX/DTX micelles are effective on inhibiting cancer cells compared with the free DTX which would be a promising carrier in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen
There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Zheng Yuhao,Sheng Fan,Wang Zihang,Yang Guang,Li Chenguang,Wang He,Song Zhiming
Advanced drug carriers for the controlled release of chemotherapeutics in the treatment of malignant tumors have drawn significant notice in recent years. In the current study, microspheres (MPs) loaded with docetaxel (DTX) were prepared using polylactic-co-glycolic acid copolymer (PLGA). The double emulsion solvent evaporation method is simple to perform, and results in high encapsulation efficiency. Electron micrographs of the MPs showed that controlling the shear rate can effectively control the size of the MPs. At present, most DTX sustained-release carriers cannot maintain stable and long-term local drug release. The 1.68 μm DTX-loaded microspheres (MP/DTX) with elastase was completely degraded in 14 d. This controlled degradation period is similar to a course of treatment for most cancers. The drug release profile of all kinds of MP/DTX demonstrated an initial rapid release, then slower and stable release to the end. The current study demonstrates that it is possible to create drug-loaded MPs with specific degradation times and drug release curves, which may be useful in achieving optimal treatment times and drug release rates for different diseases, and different drug delivery routes. The initial burst release reaches the effective concentration of the drug at the beginning of release, and then the drug concentration is maintained by stable release to reduce the number of injections and improve patient compliance.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Jinfeng Dou,Haiqun Zhang,Xiuju Liu,Mengyu Zhang,Guangxi Zhai
A mixed micelle that comprised of monomethylol poly(ethylene glycol)-poly( d , l -lactic acid) (MPP), d -α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and stearic acid grafted chitosan oligosaccharide(CSO-SA) copolymers was developed to enhance the oral absorption of docetaxel (DTX). DTX-loaded MPP/TPGS/CSO-SA mixed polymeric micelles (MPMs) were prepared with thin film hydration method and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, critical micellization concentration, and in vitro stability in media modeling physiological conditions. The in vitro release of docetaxel from the mixed micelles was studied with dialysis method. The oral bioavailability studies were conducted in rats and the pharmacokinetic parameters were evaluated. The results showed that DTX-loaded MPP/TPGS/CSO-SA MPMs had a mean diameter of 34.96 nm and exhibited spherical shape under transmission electron microscopy. The drug loading of DTX in the mixed micelles was 19.15%. The critical micellization concentration of MPP/TPGS/CSO-SA copolymer was 2.11 × 10 −5 M, and the size of mixed micelles in gastric fluid (pH 1.6) for 2 h and simulated intestinal fluid (pH 6.5) for 6 h showed no significant change. The in vitro release study showed that DTX-loaded MPP/TPGS/CSO-SA MPMs exhibited slower release characteristics compared to DTX solution. The oral bioavailability of the DTX-loaded MPP/TPGS/CSO-SA MPMs was increased by 2.52 times compared to that of DTX solution. The current results encourage further development of DTX mixed polymeric micelles as the oral drug delivery system.
研究领域:
药学
·
药物递送系统
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
iScience
·
2026
·Vol. 29
·期 6
·
IF 4.5
Wei Huang,Zhirui Tao,Xiaolin Xu,Huangming Cao,Li Cheng,Jin Li
Docetaxel (DTX) resistance limits therapeutic efficacy in gastric cancer (GC). Through RNA sequencing of DTX-resistant GC cells, we identified insulin-like growth factor-like family member 2 (IGFL2) as a key upregulated gene. We demonstrate that IGFL2 overexpression enhances GC cell proliferation, migration, and invasion while suppressing apoptosis, thereby reducing DTX sensitivity. Mechanistically, IGFL2 directly binds the Toll-like receptor 4 (TLR4) promoter, activating the TLR4/MyD88/p65 pathway and upregulating drug efflux pumps MDR1 and BCRP. Knockdown of IGFL2 resensitizes resistant cells to DTX both in vitro and in mouse xenograft models. These findings establish IGFL2 as a regulator of DTX resistance via TLR4 signaling, suggesting its relevance as a therapeutic target for overcoming chemoresistance in GC.
✓ 已验证
DOI
PubMed
高影响因子
Nanomaterials
·
2026
·Vol. 16
·期 13
·805
·
IF 4.8
Guangru Chu,Kaiyi Zhang,Yaru Wu,Siqi He,Zhongkai Liu,Aijiao Wang,Hongji Wang,Liying Cui,Shengkai Liu,Jin Huang,Jinsong Peng,Zhiguo Liu
Hollow mesoporous silica nanoparticles (HSNs) were synthesized via the Stöber method using resorcinol–formaldehyde resin as a template and further developed as a multifunctional nanocarrier for synergistic chemo–photothermal therapy. Docetaxel (DTX) and indocyanine green (ICG) were co-loaded into HSNs as the prodrug and photothermal agent. The loading sequence of these agents can critically affect encapsulation efficiency. Preloading DTX followed by ICG incorporation achieved the highest drug loading (38.65%) and preserved the photoactivity of ICG. The resulting ICG&DTX@NH2-HSNs exhibited strong and stable near-infrared photothermal conversion, as well as pH- and laser-responsive drug release behavior. In vitro studies confirmed efficient cellular uptake by 4T1 tumor cells and enhanced cytotoxicity compared with single treatments. In vivo experiments demonstrated significant tumor growth suppression in 4T1 tumor-bearing mice, with the greatest effect observed under combined ICG&DTX@NH2-HSNs and laser irradiation. Importantly, histological analysis of major organs revealed no obvious toxicity, confirming the biosafety of the present nanoplatform. This study confirmed the potential of hollow mesoporous silica-based nanocarriers as safe and effective platforms for combined chemotherapy and photothermal cancer therapy.
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 45
·2005039
·
IF 11.459
Shiyi Zuo,Bingjun Sun,Yinxian Yang,Shuang Zhou,Yu Zhang,Mengran Guo,Mengchi Sun,Cong Luo,Zhonggui He,Jin Sun
The current state of chemotherapy is far from satisfaction, restricted by the inefficient drug delivery and the off-target toxicity. Prodrug nanoassemblies are emerging as efficient platforms for chemotherapy. Herein, three docetaxel dimeric prodrugs are designed using diselenide bond, disulfide bond, or dicarbide bond as linkages. Interestingly, diselenide bond-bridged dimeric prodrug can self-assemble into stable nanoparticles with impressive high drug loading (≈70%, w/w). Compared with disulfide bond and dicarbide bond, diselenide bond greatly facilitates the self-assembly of dimeric prodrug, and then improves the colloidal stability, blood circulation time, and antitumor efficacy of prodrug nanoassemblies. Furthermore, the redox-sensitive diselenide bond can specifically respond to the overexpressed reactive oxygen species and glutathione in tumor cells, leading to tumor-specific drug release. Therefore, diselenide bond bridged prodrug nanoassemblies exhibit discriminating cytotoxicity between tumor cells and normal cells, significantly alleviating the systemic toxicity of docetaxel. The present work gains in-depth insight into the impact of diselenide bond on the dimeric prodrug nanoassemblies, and provides promising strategies for the rational design of the high efficiency–low toxicity chemotherapeutical nanomedicines.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·1383-1388
·
IF 1.692
Tao Liu,Xidong Wu,Yigang Wang,Xiongjun Hou,Gang Jiang,Ting Wu,Huifen Xie,Minqiang Xie
The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized star‑shaped co‑polymer consisting of β‑cyclodextrin (CD) and a poly(L‑lysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP‑9) small interfering RNA, via CD‑PLLD/DOC/MMP‑9 complexes, into mice implanted with HNE‑1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic co‑polymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CD‑PLLD/DOC/MMP‑9 inhibited HNE‑1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP‑9 was investigated; CD‑PLLD/DOC/MMP‑9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the blood‑brain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE‑1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2017
·Vol. 38
·期 12
·1655-1662
·
IF 3.223
Dong Xin-yue,Lang Tian-qun,Yin Qi,Zhang Peng-cheng,Li Ya-ping
Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 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）