JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Xinran Wang,Jieyi Pan,Haohui Shi,Na Liang,Shaoping Sun
This study was aimed at fabricating tumor targeting and acid-responsive micelles as carriers for paclitaxel (PTX). An amphipathic polymer TOS-Ace-PEG-Bio was designed and synthesized by conjugating α-tocopherol succinate (TOS) with biotinylated polyethylene glycol (PEG-Bio) via acetal bond. The polymer could self-assemble into nanosized micelles and encapsulate PTX. The PTX-loaded micelles possessed appropriate particle size with the mean value of 129.3 ± 0.9 nm . Strong pH dependent PTX release behavior was verified by in vitro drug release study. At cellular level, the PTX-loaded micelles could be selectively internalized by MCF-7 cells. The in vivo study also confirmed their excellent antitumor activity and reduced side effects. Based on these features, the TOS-Ace-PEG-Bio micelles were considered to be promising carriers for delivery of PTX.
研究领域:
药剂学
·
肿瘤学
·
材料科学
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产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Xiang Zhang,Yurui Xu,Wanyao Chen,Laiyou Wang,Xinghai Ning,Haixiong Ge
UV-nanoimprint lithography (UV-NIL) has been proved to be an efficient method for preparing nanodrug delivery systems. Herein, we used UV-NIL associated with the glancing angle deposition (GLAD) process of electron beam evaporation to prepare Au-coated PLGA nanocylinders loaded with PTX (PTX-PLGA-Au NCs) to enhance anticancer efficacy by the cooperative treatment of photothermal-chemotherapy. PTX-PLGA-Au NCs with different length-to-diameter ratios can be prepared by controlling the concentration of PLGA and regulating the angle of GLAD. Upon 808 nm near-infrared (NIR) irradiation, PTX-PLGA-Au NCs exhibit a stable and repeatable photothermal effect. Besides, hyperthermia generated by the Au layer on the surface of PTX-PLGA-Au NCs under laser irradiation promoted the rapid release of PTX. The in vitro studies demonstrated that PTX-PLGA-Au NCs can achieve the synergistic effect of photothermal-chemotherapy, leading to increased cell cytotoxicity. Therefore, UV-NIL combined with the GLAD process produced a promising nanofabrication method for efficiently developing a multifunctional nanoplatform for cancer treatment.
研究领域:
纳米医学
·
肿瘤学
·
药剂学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Shaojin Lu,Shiyu Zhou,Xiujuan Xiang,Biyou Zhang,Zhengyuan Xu,Qing Pei,Zhigang Xie
Improving drug delivery efficacy is the key point for enhancing the therapeutic index of medicines. Herein, we report fatty chain conjugated paclitaxel (PTX) prodrugs with a disulfide bond as linker. The formed prodrugs can self-assemble into stable nanoparticles in aqueous solutions, and rapidly transform into long-circulating nanocomplexes via the non-covalent binding to serum albumin in blood, enabling efficient drug delivery and robust antitumor effect. PTX prodrug (PC) with single-chain possess the improved self-assembly and interaction with albumins. The formed PC@albumin nanocomplexes reinforce the responsiveness of prodrug activation, and exhibit the enhanced tumor suppression ability. This strategy of hitchhiking albumin to deliver therapeutic agents holds great promise for enhanced chemotherapy.
研究领域:
药学
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纳米技术
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癌症治疗
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Jiahong Huang,De Bai,Lin Xie,Tianqi Liu,Jichuan Zhang,Zhenye Zhu,Chengyu Wu,Jiaheng Zhang
Although paclitaxel (PTX) is a broad-spectrum anticancer drug, its low water solubility, poor bioavailability, and susceptibility to drug resistance have seriously limited its application. In recent years, studies have shown that metformin has potential anti-tumor activity. This paper reports the successful loading of PTX into metformin oleate ionic liquid ([Met][Ole] IL) micelles and [Met][Ole] IL/tween 80 (T-80) micelles. The obtained PTX-IL/T-80 micelle exhibited a good particle size (5.77 nm) and stability (Zeta potential: −51.65 ± 7.73 mV) in addition to possessing in vitro and in vivo antitumor efficacy. The inhibition rate of PTX-IL/T-80 (10 ppm) on 4 T1 cells reached 93 %. Furthermore, the results of the in vivo treatment in mice revealed that the tumor inhibition rate of PTX-IL/T-80 under a small-dose treatment (0.5 mg·kg −1 ) was 37.7 %, which was much higher than that of the PTX prodrug group (11.7 %). Consequently, PTX-IL/T-80 has a great potential for its application in cancer therapy owing to the good synergistic antitumor effect between ([Met][Ole] ionic liquid and PTX.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 36
·30184-30193
·
IF 3.289
Yu Liu,Han Zhong,Yu Qin,Yan Zhang,Xinfeng Liu,Tao Zhang
Graphene oxide (GO) and reduced graphene oxide (RGO) are attractive materials due to their potential biomedical applications, especially as drug delivery vehicles because of their huge specific surface area. In the current study, GO and RGO were prepared. In addition, a perylene derivative, phosphorylcholine oligomer grafted perylene (Perylene-PCn), was synthesized following the atom transfer radical polymerization procedure. In order to determine their structures, the products were characterized carefully with Fourier transform infrared spectra, proton nuclear magnetic resonance, X-ray photoelectron spectroscopy, wide angle X-ray diffraction, thermogravimetric analysis, and atomic force microscopy etc. The properties including fluorescence and biocompatibility were also evaluated. Utilizing the π–π stacking interaction of RGO and the perylene moiety, water dispersible RGO/Perylene-PCn composites were fabricated and then investigated as a vehicle for anti-tumor paclitaxel (PTX). The anti-tumor effects of free PTX and PTX@RGO/Perylene-PCn were compared with an in vitro cytotoxicity assay. The results demonstrated that RGO/Perylene-PCn can be used as an anti-tumor agent delivery vehicle for potential oncology applications.
研究领域:
材料科学
·
生物医药工程
·
肿瘤学
✓ 已验证
DOI
高影响因子
GREEN CHEMISTRY
·
2024
·
IF 9.3
Yanhui Hu,Hua Yue,Shiqi Huang,Bingxi Song,Yuyuan Xing,Minmin Liu,Gongying Wang,Yanyan Diao,Suojiang Zhang
Paclitaxel (PTX) is a crucial medication employed in the treatment of various cancers, and its limited solubility has been a persistent clinical hurdle. Ionic liquids (ILs), considered as “green solvents”, possess remarkable attributes such as exceptional miscibility, tailorable properties, and versatility. These properties have ushered in a revolution in the realm of biomedicine, particularly in addressing the solubility challenges of poorly soluble drugs. In this work, low-toxicity diimidazolium based ILs were introduced into a PTX dissolution system for the first time. Compared to mono-imidazolium based ILs, diimidazolium based ILs exhibited lower in vitro cytotoxicity and the substitution of Cremophor EL (CrEL) with biocompatible [C10(MIM)2][Br]2 and water resulted in lower cytotoxicity at a certain concentration. Furthermore, [C10(MIM)2][Br]2 could effectively improve the solubility of PTX, and this enhancement was strongly correlated with the length of the carbon chain in the cation and the IL concentration. Significantly, the [C10(MIM)2][Br]2-based dissolution system demonstrated the capability to attain a PTX content that is on par with the widely used commercial drug Taxol. Besides, the [C10(MIM)2][Br]2–PTX complex displayed excellent physical stability for a long period of time, with no significant change of PTX concentration in the solution. Additionally, various interactions existed between [C10(MIM)2][Br]2 and PTX, encompassing hydrophobic interactions, π–π stacking, CH–π interactions, and hydrogen bonds. The results indicated that the diimidazolium based IL system showed promise as a biocompatible platform for the delivery of PTX.
研究领域:
药学
·
生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Tao Zhang,Wei Zhang,Min Zheng,Zhigang Xie
Self-assembly of organic molecules has attracted more and more attention because of precise molecular structure and multifarious synthesis chemistry . Herein, near-infrared brominated boron-dipyrromethenes (BODIPY) paclitaxel conjugate (BrBDP-2PTX) was synthesized. BrBDP-2PTX could self-assemble into uniform spherical nanoparticles (BrBDP-2PTX NPs) via nanoprecipition method. The obtained nanoparticles showed satisfying stability in aqueous solution and 10% fetal bovine serum (FBS) containing phosphoric acid buffer solution (PBS). Moreover, BrBDP-2PTX NPs could make rapid enzyme response to Proteinase K as evidenced by the obvious changes in size and size distribution. BrBDP-2PTX NPs could be internalized by the HeLa cells and exhibited potent cytotoxicity toward tumor cells (human cervical carcinoma cells and liver hepatocellular carcinoma cells) as revealed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays and live/dead staining. Furthermore, in vivo experiments indicated BrBDP-2PTX NPs could be used as efficient bioimaging agents without causing any systemic toxicity. This work highlights the potential of using self-assembly of small organic molecules to develop functional nanomaterials .
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Like Ning,Chaoqun You,Yu Zhang,Xun Li,Fei Wang
Hydrogel for various applications, such as cell encapsulation and controlled release of drugs, has attracted the field of biomaterials in the past decades. Specially, research on the surface-modified nanocellulose hydrogel has grown rapidly on account of the importance of target delivery in the anti-cancer therapy. In this work, surface-modified nanocellulose was mixed with hexadecyl amine as long chains to blend to build a network to produce hydrogel, which was successfully developed for controlled and targeted delivery of paclitaxel. The pH-stimuli surface-modified nanocellulose hydrogel was characterized and biological evaluated in vitro. The hydrogel was stable at pH 7.4 and paclitaxel was released by the shape change of hydrogel in an acidic environment (pH 5.5), and the sustained release of paclitaxel was observed at pH 5.5. The vitro cytotoxicity studies indicated that the drug accumulation and the inhibition of A549 and HepG2 cells was effectively increased by the surface-modified nanocellulose hydrogel as compared with free paclitaxel. The inhibitory effect of A549 cells was improved by nearly 30% as compared with free paclitaxel and the apoptosis rate was up to 90.5% after 12 h incubation. In addition, the inversion test and the results of a series of cell experiments in vitro demonstrated a good performance of the surface-modified nanocellulose hydrogel.
研究领域:
生物材料
·
药剂学
·
癌症研究
·
药物递送系统
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DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 3
·180-186
·
IF 1.164
Zi-Ming Zhao,Yu Wang,Jin Han,Hui-Dong Zhu,Lin An
Two types of amphoteric calix[n]arene carboxylic acid (CnCA) derivative, i.e., calix[6]arene hexa-carboxylic acid (C6HCA) and calix[8]arene octo-carboxylic acid (C8OCA), were synthesized by introducing acetoxyls into the hydroxyls of calix[n]arene (n=6, 8). C6HCA and C8OCA nanoparticles (NPs) were prepared successfully using the dialysis method. CnCA NPs had regular spherical shapes with an average diameter of 180–220 nm and possessed negative charges of greater than −30 mV. C6HCA and C8OCA NPs were stable in 4.5% bovine serum albumin solutions and buffers (pH 5–9), with a low critical aggregation concentration value of 5.7 mg·L−1 and 4.0 mg·L−1, respectively. C6HCA and C8OCA NPs exhibited good paclitaxel (PTX) loading capacity, with drug loading contents of 7.5% and 8.3%, respectively. The overall in vitro release behavior of PTX from the CnCA NPs was sustained, and C8OCA NPs had a slower release rate compared with C6HCA NPs. These favorable properties of CnCA NPs make them promising nanocarriers for tumor-targeted drug delivery.
研究领域:
药剂学
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2019
·
IF 4.716
Zeng Qiong-zhen,Yang Fan,Li Chen-guang,Xu Li-hui,He Xian-hui,Mai Feng-yi,Zeng Chen-ying,Zhang Cheng-cheng,Zha Qing-bing,Ouyang Dong-yun
Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer therapy, has any influences on NLRP3 inflammasome activation. Here we showed that paclitaxel pre-treatment greatly enhanced ATP- or nigericin-induced NLRP3 inflammasome activation as indicated by increased release of cleaved caspase-1 and mature IL-1β, enhanced formation of ASC speck, and increased gasdermin D cleavage and pyroptosis. Paclitaxel time- and dose-dependently induced α-tubulin acetylation in LPS-primed murine and human macrophages and further increased ATP- or nigericin-induced α-tubulin acetylation. Such increased α-tubulin acetylation was significantly suppressed either by resveratrol or NAD+ (coenzyme required for deacetylase activity of SIRT2), or by genetic knockdown of MEC-17 (gene encoding α-tubulin acetyltransferase 1). Concurrently, the paclitaxel-mediated enhancement of NLRP3 inflammasome activation was significantly suppressed by resveratrol, NAD+, or MEC-17 knockdown, indicating the involvement of paclitaxel-induced α-tubulin acetylation in the augmentation of NLRP3 inflammasome activation. Similar to paclitaxel, epothilone B that is another microtubule-stabilizing agent also induced α-tubulin acetylation and increased NLRP3 inflammasome activation in macrophages in response to ATP treatment. Consistent with the in vitro results, intraperitoneal administration of paclitaxel significantly increased serum IL-1β levels, reduced bacterial burden, dampened infiltration of inflammatory cells in the liver, and improved animal survival in a mouse model of bacterial infection. Collectively, our data indicate that paclitaxel potentiated NLRP3 inflammasome activation by inducing α-tubulin acetylation and thereby conferred enhanced antibacterial innate responses, suggesting its potential application against pathogenic infections beyond its use as a chemotherapeutic agent.
研究领域:
免疫学
·
药理学
·
传染病学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Qianqian Qi,Zhanyu Zhang,Dun Wang
The lack of targeting and poor solubility of anti-tumor drugs are two major limitations to the outcome of tumor therapy. To address the inherent drawbacks, we designed a novel prodrug of paclitaxel (PTX), HP-PTX. This HP-PTX prodrug contains a PEGylated heptamethylene cyanine dye (PEG-IR808–1) that was conjugated to PTX via a redox-sensitive disulfide bond. The moiety of IR808–1 acts as a tumor-targeting ligand, enabling HP-PTX not only to target tumor cells, but also to localize to mitochondria and generate ROS under 808 nm laser irradiation to wound cellular mitochondria thus exerting cytotoxic effect. Meanwhile, in vitro cellular uptake assays showed that HP-PTX possesses MCF-7 cell tumor targeting specificity which was attributed to the preferential uptake of heptamethine cyanine dye mediated by the overexpressed organic anion-transporting polypeptides (OATP) on MCF-7 cell membrane. Near-infrared in vivo imaging showed that incorporation of polyethylene glycol effectively prolonged prodrug's half-life in vivo. In addition, in vivo experiments showed that with combinational therapy strategy HP-PTX was able to kill cancer cells with high efficiency (69.52 %) without notable toxic side effects compared to PTX. These results are evidence of the potential of the tumor-targeting prodrug HP-PTX for the treatment of breast cancer.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS Journal
·
2026
·Vol. 28
·期 5
·133
·
IF 3.4
Luo Haozhong,Pan Wenxiu,Liu Wenxue,Zhang Yuchen,Zou Meijuan,Piao Hongyu
To address the challenges associated with keloid pharmacotherapy, we developed a melittin (MEL)-modified paclitaxel (PTX) liposomal delivery system as a reconstitutable lyophilized formulation intended for subcutaneous injection. MEL, an amphipathic membrane-active peptide, was incorporated as a functional component to enhance liposome-cell interactions and facilitate intracellular delivery of PTX. This design aimed to improve the in vitro anti-keloid activity of PTX liposomes while providing a lyophilized injectable formulation suitable for reconstitution before use. After MEL modification, the zeta potential shifted upward with increasing MEL content, supporting MEL surface modification of PTX liposomes through electrostatic interactions. Moreover, freeze-dried MEL-modified PTX liposomes showed comparable particle size, zeta potential, and release behavior to the original liposomes. Although the encapsulation efficiency (EE%) of PTX and the modification efficiency (ME%) of MEL were slightly reduced after lyophilization, the formulation maintained good storage stability at 4 ± 2°C for 6 months. Confocal microscopy and flow cytometry analyses using coumarin 6 (C6) instead of PTX showed enhanced cellular uptake in human keloid fibroblasts (HKF). The CCK-8 assay indicated that although MEL-Liposome (600:1) alone did not obviously inhibit HKF proliferation under the tested conditions, MEL-PTX-Liposome (600:1) showed significantly stronger antiproliferative activity than PTX-Liposome. Specifically, MEL-PTX-Liposome (600:1) reduced HKF cell migration to 16.8% (control, 92.6%; PTX-Liposome, 36.9%), representing a significant improvement over PTX-Liposome. These findings support MEL-modified PTX liposomes as a promising reconstitutable lyophilized injectable formulation for subcutaneous anti-keloid therapy and provide a formulation basis for further translational development. Graphical
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DOI
高影响因子
危险品化学品经营许可证（带存储）