BIOMACROMOLECULES
·
2016
·
IF 5.583
Pei Zhang,Huiyuan Zhang,Wenxiu He,Dujuan Zhao,Aixin Song,Yuxia Luan
Here, we prepared novel redox-sensitive drug delivery system based on copolymer-drug conjugates methoxy poly(ethylene glycol)-poly(γ-benzyl l-glutamate)-disulfide-docetaxel (mPEG-PBLG-SS-DTX) to realize the desirable cancer therapy. First, copolymers of methoxy poly(ethylene glycol)-poly(γ-benzyl l-glutamate) (mPEG-PBLGs) with different molecular weight (mPEG2000-PBLG1750 and mPEG5000-PBLG1750) were synthesized via the ring open polymerization (ROP) of 5-benzyl-l-glutamate-N-carboxyanhydride (γ-Bzl-l-Glu-NCA) initiated by monoamino-terminated mPEG (mPEG-NH2). Then, the docetaxel (DTX) was conjugated to the block polymers through a linkage containing disulfide bond to obtain mPEG-PBLG-SS-DTXs, including mPEG2000-PBLG1750-SS-DTX and mPEG5000-PBLG1750-SS-DTX. The obtained copolymer-drug conjugates mPEG2000-PBLG1750-SS-DTX and mPEG5000-PBLG1750-SS-DTX could self-assemble into nanosized micelles in aqueous environment via dialysis method with a low critical micelle concentration (CMC, 3.98 and 6.94 μg/mL, respectively). The size of the micelles was approximately 101.3 and 148.9 nm, respectively, with a narrow size distribution. They released approximately 40% DTX in a sustained way in the presence of 50 mM DTT after 120 h in comparison with only approximately 10% DTX released from micelles in the absence of DTT. The high cytotoxicity was identified for mPEG-PBLG-SS-DTXs micelles against MCF-7/ADR and A549 cells, and the IC50 of mPEG-PBLG-SS-DTXs micelles against MCF-7/ADR for 24 h was roughly a 15th of the value of free DTX. Moreover, the mPEG-PBLG-SS-DTXs micelles could be efficiently uptaken by MCF-7/ADR and A549 cells. Thus, the present constructed mPEG-PBLG-SS-DTXs micelles were very promising for effective cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Current Drug Delivery
·
2024
·Vol. 21
·期 5
·775-784
·
IF 2.8
Lv Hongshuai,Jia Weiping,Dong Peng,Liu Jiaojiao,Wang Si,Li Xiaohai,Hu Jinghua,Zhao Ling,Shi Yikang
Background: Most chemotherapeutic agents are characterized by poor water solubility and non-specific distribution. Polymer-based conjugates are promising strategies for overcoming these limitations.Objective: This study aims to fabricate a polysaccharide, dextran-based, dual-drug
conjugate by covalently grafting docetaxel (DTX) and docosahexaenoic acid (DHA) onto the bifunctionalized dextran through a long linker, and to investigate the antitumor efficacy of this conjugate against breast cancer.Methods: DTX was firstly coupled with DHA and covalently bounded with
the bifunctionalized dextran (100 kDa) through a long linker to produce a conjugate dextran-DHA-DTX (termed C-DDD). Cytotoxicity and cellular uptake of this conjugate were measured in vitro. Drug biodistribution and pharmacokinetics were investigated through liquid chromatography/mass
spectrometry analysis. The inhibitory effects on tumor growth were evaluated in MCF-7- and 4T1-tumor-bearing mice.Results: The loading capacity of the C-DDD for DTX was 15.90 (weight/weight). The C-DDD possessed good water solubility and was able to self-assemble into nanoparticles measuring
76.8 ± 5.5 nm. The maximum plasma concentration and area under the curve (0-∞) for the released DTX and total DTX from the C-DDD were significantly enhanced compared with the conventional DTX formulation. The C-DDD selectively accumulated in the tumor, with limited distribution
was observed in normal tissues. The C-DDD exhibited greater antitumor activity than the conventional DTX in the triplenegative breast cancer model. Furthermore, the C-DDD nearly eliminated all MCF-7 tumors in nude mice without leading to systemic adverse effects.Conclusion: This dual-drug
C-DDD has the potential to become a candidate for clinical application through the optimization of the linker.
研究领域:
药理学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Lekang Liu,Mingbo Shao,Luoyuan Guo,Wenjun Wang,Xiuwen Zheng,Xiaolei Jiang
We have developed an innovative Cu-doped and DTX-loaded Cu-MnO2@DTX@FA (MCDF) nanodrug designed to strategically alter tumor microenvironment (TME) by harnessing the synergistic effects of chemodynamic therapy (CDT), chemotherapeutic agents, and the induction of ferroptosis and cuproptosis. The MCDF nanodrug efficiently degrades, releasing abundant Mn4+, Cu2+, and DTX. The conversion of Cu2+ to Cu+ facilitated by FDX1 initiates cuproptosis, while, similar to Mn2+, Cu+ reacts with hydrogen peroxide (H2O2) to generate hydroxyl radicals (·OH). Cu2+ and Mn4+ oxidize glutathione (GSH), significantly depleting GSH levels in tumor cells and inactivating GPX4, which further promotes ferroptosis. The release of Cu2+ and Mn4+ intensifies the cuproptosis. DTX effectively disrupts the cell division cycle, thereby inhibiting the proliferation and spread of tumor cells. The FA-modified MCDF is designed to evade immune detection while selectively targeting tumor tissues, ensuring precision in treatment delivery. This cutting-edge material not only provides a multifunctional therapeutic strategy but also sets the stage for the next generation of tumor-targeting nanomedicines.
研究领域:
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2024
·
IF 3.6
Junjie Ye,Qi Wu,Qingfen Ji,Shengjie You,Song Gao,Guanan Zhao,Qiangqiang Xu,Ken Liu,Peng Li
Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.
研究领域:
癌症研究
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2024
·Vol. 86
·期 1
·e70043
·
IF 3.5
Qingqing Li,Yufeng Liu,Yilin Cheng,Huaibao Cao,Kunda Du,Tianyu Zhu,Defeng Xu,Hang Hu
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug docetaxel (DTX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. In the present research, DTX is condensed with 3-(pyridin-2-yldisulfanyl) propanoic acid via ester bond to obtain the intermediate Py-SS-DTX. Two conjugates GSS-DTX and RGDC-SS-DTX were obtained by conjugation of Py-SS-DTX with glutathione (GSH) and RGDC peptide through a thiol-disulfide exchange reaction. Afterwards, these two peptide–DTX conjugates were characterized by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. The GSS-DTX and RGDC-SS-DTX were further evaluated in terms of drug release, cell cycle inhibition, cell apoptosis, and cytotoxicity. The results show that both the GSS-DTX and RGDC-SS-DTX exhibit reduction-responsive drug release and RGDC-SS-DTX exhibit higher reduction-responsiveness. The in vitro antitumor activity study shows that RGDC-SS-DTX exhibits enhanced G2/M phase arrest, cell apoptosis rate, and cytotoxicity as compared to GSS-DTX and free DTX. Besides, RGDC-SS-DTX shows reduced cytotoxicity on normal cells as compared to free DTX. The RGDC-SS-DTX synthesized in this study represents a novel DTX conjugate to effectively and selectively inhibit tumor cells.
研究领域:
药学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Yuqian Du,Chutong Tian,Menglin Wang,Di Huang,Wei Wei,Yan Liu,Lin Li,Bingjun Sun,Longfa Kou,Qiming Kan,Kexin Liu,Cong Luo,Jin Sun,Zhonggui He
Oligopeptide transporter 1 (PepT1) has been a striking prodrug-designing target. However, the underlying mechanism of PepT1 as a target to facilitate the oral absorption of nanoparticles (NPs) remains unclear. Herein, we modify Poly (lactic-co-glycolic acid) (PLGA) NPs with the conjugates of dipeptides (L-valine-valine, L-valine-phenylalanine) and polyoxyethylene (PEG Mw: 1000, 2000) stearate to facilitate oral delivery of docetaxel (DTX) to investigate the oral absorption mechanism and regulatory effects on PepT1 of the dipeptide-modified NPs. The cellular uptake of the dipeptide-modified NPs is more efficient than that of the unmodified NPs in the stably transfected hPepT1- Hela cells and Caco-2 cells, suggesting the involvement of PepT1 in the endocytosis of NPs. The internalization of the dipeptide-modified NPs is proved to be a proton-dependent process. Moreover, the L-valine-valine modified NPs with shorter PEG chain exhibit distinct advantages in terms of intestinal permeability and oral absorption, resulting in significantly improved oral bioavailability of DTX. In summary, PepT1 could serve as a desirable target for oral nanoparticulate drug delivery and the dipeptide-modified NPs represent a promising nanoplatform to facilitate oral delivery of hydrophobic drugs with low bioavailability.
研究领域:
药剂学
·
纳米医学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Wenjia Wang,Xiaoqin Zhang,Zhiqian Li,Dayi Pan,Hongyan Zhu,Zhongwei Gu,Jie Chen,Hu Zhang,Qiyong Gong,Kui Luo
To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli-responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSH-responsive disulfide bonds , and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2020
·Vol. 11
·期 3
·1133-1143
·
IF 2.664
Li Ruirui,Shan Linwei,Yao Yanan,Peng Feifei,Jiang Shanshan,Yang Dandan,Ling Guixia,Zhang Peng
The platform of the combination chemo-photodynamic therapy has received widespread attention for enhancing anticancer efficacy and inhibiting tumor growth, which supports thermosensitive and controlled drug release. Here, an injectable thermoreversible hydrogel (BPNSs/DTX-M-hydrogel) co-encapsulating black phosphorus nanosheets (BPNSs) and docetaxel (DTX) micelles was prepared to increase drug accumulation in tumor tissue and improve anticancer efficacy. BPNSs were prepared by liquid exfoliation method with a simple and rapid preparation, and DTX micelles were prepared by the thin film dispersion method. Hydrogel was prepared with F127 as hydrogel matrix for intratumoral injection. BPNSs, DTX micelles, and BPNSs/DTX-M-hydrogel were characterized by particle size, morphology, stability and degradation, phase transition feature, and photodynamic performance. And the in vivo anticancer efficacy was evaluated in 4T1 tumor-bearing Balb/c mice. The results showed that the particle size of DTX micelles and BPNSs were about 16 and 180 nm, respectively. The hydrogel with the transformation temperature at near body exhibited great photodynamic efficacy and good biodegradability. Moreover, BPNSs/DTX-M-hydrogel with the combination of chemotherapy and photodynamic therapy exhibited unique anticancer efficacy with low toxicity. In conclusion, the combination platform of chemo-photodynamic therapy based on BPNSs could be a prospective strategy in antitumor research.
Graphical abstract
研究领域:
肿瘤学
·
药剂学
·
材料科学
✓ 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
JOURNAL OF NANOPARTICLE RESEARCH
·
2014
·Vol. 16
·期 12
·1-11
·
IF 2.278
Huang Xiao,Wang Zhen,Dai Hong,Wang Chunmei,Xia Bing,Chen Lan,Pan Jun
Although urethral carcinoma has a low incidence, it suffers from a poor curative rate for the low retention of medicine around urethra. In the present study, we developed a kind of magnetic targeting perfusion chemotherapy to detain the chemotherapeutic drugs. Docetaxel (TXT) grafted magnetic nanoparticles, of which size was around 40 nm, were obtained by the conjugation of TXT to amino-functionalized iron oxide (NH 2 @Fe 3 O 4 ). They have shown great potential to be targeted to and stayed in desired position of urethra under the externally applied magnetism through in vitro mimic urethral study. Furthermore, they have validly inhibited the growth of direct-contacted human urethral squamous carcinoma cells in vitro (up to 56.34 %) by the combination effects of TXT and NH 2 @Fe 3 O 4 , however, less than 3 % of TXT released from the nanoparticles, which was very few to impair the adjacent normal cells and tissues. Therefore, this kind of novel agentia was expected to hold great potential in clinic urethral carcinoma therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Medical Sciences
·
2017
·
IF 2.399
Lin Yu,Xiaofeng Wu,Min Chen,Huarong Huang,Yan He,Huaqian Wang,Dongli Li,Zhiyun Du,Kun Zhang,Susan Goodin,Xi Zheng
Background : Docetaxel is the first-line treatment for castration-resistant prostate cancer (CRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminishes its efficacy in high-dose monotherapy. YK-4-279 is a small molecule inhibitor of ETV1 that plays an important role in the progression of prostate cancer. The aim of this study was to evaluate the hypothesis that the combination of docetaxel and YK-4-279 will have a synergistic effect on inhibiting growth and accelerating apoptosis in human prostate cancer cells. Methods : Cell growth assessed using CCK-8 and trypan blue exclusion assays. Cell apoptosis was determined by morphological assessment in cells stained with propidium iodide. Standard scratch migration and Matrigel-coated transwell invasion assays were used to assess cell migration and invasion, respectively. Western blotting was used to investigate the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in prostate cancer cells. Results : The combination of low-dose docetaxel and YK-4-279 synergistically inhibited growth and induced apoptosis in human prostate cancer cells. The combination also more efficiently suppressed the migration and invasion of LNCaP and PC-3 cells. The combination of low-dose docetaxel and YK-4-279 caused a stronger decrease in the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in LNCaP cells and of p-Akt, Bcl-2, and p-STAT3 in PC-3 cells compared with either drug alone. Conclusions : These data suggest that the combination of docetaxel and YK-4-279 may be an effective approach for inhibiting the growth and metastasis of prostate cancer. This could permit a decrease in the docetaxel dose necessary for patients with CRPC and thereby lower its systemic toxicity.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Applied Ceramic Technology
·
2013
·Vol. 12
·期 2
·300-305
·
IF 1.153
Chao Yang,Lina Han,Fei Ma,Lin Zhou,Jiahong Zhou,Shaohua Wei,Guiqin Huang,Jian Shen,Fuyou Li
A new docetaxel (DTX) delivery system has been prepared based on calcium phosphate nanoparticles (CaP NPs) and obtained DTX-adsorbed CaP NPs. The DTX-adsorbed CaP NPs were nearly spherical with mean diameter about 200 nm and a negative zeta potential of −18.8 ± 0.5 mV. They can be well dispersed and stable in water for a long time. In addition, the DTX-adsorbed CaP NPs showed higher cytotoxicity in human nonsmall-cell lung cancer (NSCLC) cell lines than that of DTX at the same experimental conditions. Thus, it could be concluded that CaP NPs can be a promising DTX delivery vehicle in NSCLC chemotherapy.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）