MOLECULAR AND CELLULAR PROBES
·
2019
·
IF 2.511
Jilian Su,Junmei Wang,Jiamin Luo,Haili Li
Aims Vascular endothelial growth factor (VEGF) can promote cell division, proliferation and migration. In this study, we aimed to investigate roles of ultrasound-mediated destruction of VEGF-targeted and paclitaxel (PTX)-loaded lipid microbubbles (VTPLLM + US) in human breast cancer cells . Methods The activity of MCF-7 cells was determined by cell counting Kit-8. Flow cytometry was performed to detect the cells apoptosis and cell cycle. The expression of cell cycle-associated proteins, matrix metalloprotein-9 (MMP-9), VEGF and apoptosis-associated proteins were detected by qRT-PCR and Western blot . Results The obtained data suggested that VTPLLM + US promoted the G1 phase cell cycle arrest and suppressed the viability of MCF-7 cells. We also found that VTPLLM + US accelerated cells apoptosis. Cell cycle-associated proteins and VEGF expression were modulated by VTPLLM + US. Moreover, VTPLLM + US was found to regulate the expression levels of apoptosis-associated proteins in MCF-7 cells. Our findings suggested that VTPLLM + US suppressed the proliferation and accelerated the apoptosis of MCF-7 cells through regulating VEGF expression. Conclusions The potential effects of VTPLLM + US on apoptosis of MCF-7 cells suggest that applying VTPLLM + US might be an effective strategy in breast cancer therapies.
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高影响因子
Nanoscale
·
2025
·
IF 5.1
Yuan Quan,Yan Yuan,Kejin Chen,Ting Li,Jing Li,Mengxing Zhang,Rongying Shi,Shanshan He,Lin Li,Xun Sun,Tao Gong,Ling Zhang,Zhirong Zhang,Qing Lin
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high recurrence rates, limited therapeutic options, and a strong propensity for spontaneous lung metastasis. Increasing evidence indicates that neutrophil extracellular traps (NETs) significantly promote TNBC progression, immune evasion, and metastatic dissemination, highlighting NETs inhibition as a promising therapeutic strategy. Herein, we developed a dual pH/ROS-responsive nanoplatform (pH/ROS@(PTX/SIV)) constructed from acetylated dextran (Ace-DEX) and phenylboronic acid-modified dextran (PBAP-DEX), and further functionalized with the fibronectin-targeting peptide CREKA to achieve tumor-specific accumulation. The nanoplatform enables controlled, microenvironment-responsive release of paclitaxel (PTX) and the neutrophil elastase inhibitor sivelestat (SIV) in acidic and oxidative tumor tissues. The optimized nanoparticles exhibited uniform size, high encapsulation efficiencies, and robust dual-responsive drug release. In vitro, CREKA modification markedly enhanced cellular uptake and tumor-targeting efficiency, while the dualloaded system showed superior cytotoxicity against TNBC cells. In orthotopic TNBC mouse models, pH/ROS@(PTX/SIV) significantly suppressed primary tumor growth, prolonged survival, and critically inhibited spontaneous lung metastasis.Mechanistically, the formulation effectively blocked NETs formation both in isolated primary neutrophils and in tumor tissues, thereby disrupting NETs-mediated prometastatic signaling. Furthermore, the nanoplatform displayed favorable systemic safety with negligible organ toxicity. This dual-responsive, NET-modulating nanoplatform provides a potent and safe therapeutic strategy for combating TNBC and preventing its metastasis, offering strong potential for clinical translation.
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高影响因子
Molecular Medicine Reports
·
2014
·Vol. 11
·期 4
·2413-2420
·
IF 1.484
Jing Ma,Ling Xi Xing,Ming Shen,Fan Li,Ming Jie Zhu,Li Fang Jin,Zhaojun Li,Feng Gao,Yijin Su,You Rong Duan,Lian Fang Du
A combination of diagnostic and therapeutic ultrasound (US) techniques may be able to provide the basis of specific therapeutic protocols, particularly for the treatment of tumors. Nanotechnology may aid the progression towards the use of US for tumor diagnosis and targeted therapy. The current study investigated in vivo and in vitro US contrast imaging using nanocapsules (NCs), and also US and US‑targeted microbubble destruction (UTMD) therapy using drug‑loaded NCs for pancreatic cancer in vitro. In the current study, the NCs were made from the polymer nanomaterial poly(lactic‑co‑glycolic acid)‑monomethoxypoly(ethylene glycol) (PLGA‑mPEG), encapsulated with paclitaxel (PTX), to create PTX‑PLGA‑mPEG NCs. The PTX‑PLGA‑mPEG NCs were used as a US contrast agent (UCA), which produced satisfactory US contrast‑enhanced images in vitro and in vivo of the rabbit kidneys, with good contrast compared with lesions in the peripheral regions. However, clear contrast‑enhanced images were not obtained using PTX‑PLGA‑mPEG NCs as a UCA, when imaging the superficial pancreatic tumors of nude mice in vivo. Subsequently, fluorescence and flow cytometry were used to measure the NC uptake rate of pancreatic tumor cells under various US or UTMD conditions. An MTT assay was used to evaluate the efficiency of PTX and PTX‑PLGA‑mPEG NCs in killing tumor cells following 24 or 48 h of US or UTMD therapy, compared with controls. The specific US or UTMD conditions had been previously demonstrated to be optimal through repeated testing, to determine the conditions by which cells were not impaired and the efficiency of uptake of nanoparticles was highest. The current study demonstrated high cellular uptake rates of PLGA‑mPEG NCs and high tumor cell mortality with PTX‑PLGA‑mPEG NCs under US or UTMD optimal conditions. It was concluded that the use of NCs in US‑mediated imaging and antitumor therapy may provide a novel application for US.
研究领域:
医学影像
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肿瘤学
·
纳米医学
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PubMed
高影响因子
Nanomedicine
·
2023
·
IF 5.5
Siying Wang,Feng Han,Lanlan Xie,Yanjie Liu,Qilei Yang,Dongmei Zhao,Xiuhua Zhao
Aim: To formulate and assess the anticancer effect of the poly(lactic-co-glycolic acid) (PLGA) copolymer with the thioether groups (diethyl sulfide [Des]) and disulfide bond (cystamine containing disulfide [Cys]), which encapsulated the anticancer drug paclitaxel (PTX) and triggered PTX release in cancer cell H2O2-rich or glutathione-rich surroundings. Methods: PLGA-b-P (Des@Cys) and PLGA-b-P nanoparticles loaded with PTX were prepared and characterized in vitro. The delivery ability of the PLGA-b-P nanoparticles and PLGA-b-P-PTX nanoparticles was assessed on a CT26 (mouse colon cancer cell line) and mouse lung cancer LLC model. Results: The nanoparticles were successfully prepared. Compared with free PTX, the formulated PLGA-b-P nanoparticles loaded with PTX exhibited greater accumulation at the tumor site in the mouse model. Conclusion: PLGA-b-P nanoparticles promote drug accumulation at tumor sites, providing an effective strategy for an intelligent, responsive drug-delivery system.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-19
·
IF 10.435
Guo Weihong,Chen Zhian,Feng Xiaoli,Shen Guodong,Huang Huilin,Liang Yanrui,Zhao Bingxia,Li Guoxin,Hu Yanfeng
Background Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp.Results In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity.Conclusion sIn conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.Graphic Abstract
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高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 9
·2360-2374
·
IF 5.831
Dong Zhang,Jincheng Yang,Jibin Guan,Bin Yang,Shenwu Zhang,Mengchi Sun,Ruitao Yang,Tao Zhang,Ruoshi Zhang,Qiming Kan,Haotian Zhang,Zhonggui He,Lei Shang,Jin Sun
Prodrug self-nanoassemblies have many advantages for anticancer drug delivery, including high drug loading rate, resistance to recrystallization, and on-demand drug release. However, few studies have focused on their protein corona, which is inevitably formed after entering the blood and determines their subsequent fates in vivo. To actively tune the protein corona of prodrug nanoassemblies, three maleimide-paclitaxel prodrugs were synthesized via different redox-sensitive linkers (ester bond, thioether bond and disulfide bond). After incubation with rat plasma, the surface maleimide groups effectively captured albumins, resulting in albumin-enriched protein corona. The recruited albumin corona enabled enhanced tumor accumulation and facilitated cellular uptake, ensuring the high-efficiency delivery of nanoassemblies to tumor cells. Surprisingly, we found that the traditionally reduction-sensitive disulfide bond could also be triggered by reactive oxygen species (ROS). Such a redox dual-responsive drug release property of the disulfide bond-containing prodrug nanoassemblies further increased the selectivity in cytotoxicity between normal and tumor cells. Moreover, the disulfide bond-containing prodrug nanoassemblies exhibited the highest antitumor efficacy in vivo compared to marketed Abraxane® and other prodrug nanoassemblies. Thus, the fabrication of the maleimide-decorated disulfide bond bridged prodrug nanoassembly, integrating a tunable protein corona and on-demand drug release, is a promising strategy for improved cancer chemotherapy.
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高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Yanqiu Zhang,Lianjun Peng,Jiahui Chu,Ming Zhang,Lizhu Sun,Bin Zhong,Qiyong Wu
Background Co-delivery all-trans-retinoic acid (ATRA) and paclitaxel (PTX) is an effective strategy for cancer therapy. However, in many previous reported ATRA conjugated co-delivery systems, the ATRA was released slower than PTX, and the total drug release of ATRA far lower than that of PTX.Purpose We designed and prepared a pH and redox dual responsive drug delivery system (DA-ss-NPs) co-delivery ATRA and PTX for cancer therapy. The surface charge of DA-ss-NPs could change from negative to positive under tumor slightly acidic microenvironment, and both drugs could be quickly released from DA-ss-NPs under intracellular high concentration of glutathione (GSH).Methods The DA-ss-NPs were constructed by encapsulating PTX into the hydrophobic core of the polymer micelles, in which the polymer was synthesized by conjugating ATRA and 2,3-Dimethylmalefic anhydride (DMA) on side chains of Cystamine dihydrochloride (Cys) modified PEG-b-PAsp (named DA-ss-NPs). The surface charge of DA-ss-NPs under different pH conditions were detected. And the drug release was also measured under different concentration of GSH. The therapeutic effect of DA-ss-NPs were investigated in Human lung cancer A549 cells and A549 tumor-bearing mice.Results The zeta potential of DA-ss-NPs was -16.3 mV at pH 7.4, and which changed to 16 mV at pH 6.5. Cell uptake experiment showed that more DA-ss-NPs were internalized by A549 cells at pH 6.5 than that at pH 7.4. In addition, in presence of 10 mM GSH at pH 7.4, about 75%-85% ATRA was released from DA-ss-NPs within 48 h; but less than 20% ATRA was released without GSH. In vivo antitumor efficiency showed that the DA-ss-NPs could affectively inhibite the tumor in compared with control groups.Conclusion The charge-reversal and GSH-responsive DA-ss-NPs provide an excellent platform for potential tumor therapy.
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高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Wentao Deng,Juhui Qiu,Shaoting Wang,Zhi Yuan,Yuefeng Jia,Hailin Tan,Jiru Lu,Ruqiang Zheng
In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.
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高影响因子
JOURNAL OF DRUG TARGETING
·
2026
·
IF 4.7
Minhua Lin,Yangcheng He,Xiansheng Zhu,Jianhua Liu
Insufficient drug delivery remains a major challenge in solid tumour therapy. Ultrasound-targeted microbubble destruction (UTMD) can modulate the tumour microenvironment and improve intratumoral drug delivery. This study evaluated the acute effects of UTMD on tumour interstitial fluid pressure (IFP) and the distribution of doxorubicin and nab-paclitaxel in an MCF7-derived orthotopic breast cancer model. IFP was measured approximately 2 min after treatment. Significant IFP reductions were observed in the doxorubicin-USMB, nab-paclitaxel-USMB, and USMB-alone groups, indicating that UTMD itself contributes to the acute pressure response. Fluorescence imaging showed increased doxorubicin-associated signal in both peripheral and central tumour regions after UTMD, whereas Cy5-labeled nab-paclitaxel increased mainly in the tumour periphery. H&E staining revealed vascular dilation, erythrocyte extravasation, and microthrombus formation after USMB treatment. These findings suggest that UTMD reduces tumour IFP and alters intratumoral drug distribution, particularly in peripheral regions. However, because the two drugs differ in multiple physicochemical and formulation properties and antitumour efficacy was not assessed, their distribution differences cannot be attributed solely to size or interpreted as evidence of improved therapeutic efficacy.
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高影响因子
TALANTA
·
2016
·
IF 4.035
Dan Li,Zhonglian Cao,Xueling Liao,Ping Yang,Li Liu
Paclitaxel is a broad-spectrum anti-cancer drug by targeting microtubulin. However, multidrug resistant (MDR) makes its clinical application more difficult and results in failure of chemotherapy. Tetrandrine as a potential multidrug resistant modulator could be combined with other anti-cancer drugs. In this study, ultra-performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight mass spectrometry (QTOF) was applied to simultaneously qualitative and quantitative analysis of paclitaxel for the pharmacokinetic studies while combined with tetrandrine. This method was developed based on non-target screening mode IDA (Information Dependent Acquisition). As a result, the validated range was 0.25–64 ng/ml (30 µl plasma) for paclitaxel. Totally 33 metabolites of paclitaxel and tetrandine were identified in vivo and in vitro. The main metabolites of PTX were dose-dependent decreased with different amounts of tetrandine co-administration no matter in vivo and in vitro, the exposure of PTX increased in pharmacokinetic study. The verified method is sensitive accurate and effective for the simultaneous determination of paclitaxel and its metabolites in blood, urine and live microsome incubation samples and it was successfully applied to evaluate the pharmacokinetics and drug–drug interaction between paclitaxel and tetrandine. Furthermore, a biosensor technology, surface plasmon resonance (SPR) analysis was applied to preliminary evaluate the competitive protein binding of multiple components. The SPR analysis indicated that the affinity between 6-hydroxy-paclitaxel and micotubulin is similar to that between paclitaxel and micotubulin, and tetrandrine also does not form a competitive combination with paclitaxel. For human, 6-hydroxy-paclitaxel is the one of main metabolites of paclitaxel, so the results suggested that tetrandine has an influence on the metabolite of paclitaxel, but tetrandine and the main metabolites of PTX probably do not affect PTX's biological targeting, the effect of its pharmacological action needs to be further studied.
研究领域:
药理学
·
分析化学
·
肿瘤学
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高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 7
·1874
·
IF 5.4
Heming Zhao,Liming Gong,Hao Wu,Chao Liu,Yanhong Liu,Congcong Xiao,Chenfei Liu,Liqing Chen,Mingji Jin,Zhonggao Gao,Youyan Guan,Wei Huang
Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.Keywords:metal-organic framework;paclitaxel;peptide dimer;prostate cancer
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Hao Li,Wenbo Xie,Lei Zeng,Wen Li,Boan Shi,Fuhou Lei
Paclitaxel (PTX) is a complex diterpenoid anticancer drug whose separation from yew biomass poses a significant challenge. In this study, a new stationary phase comprising hydrogenated rosin (β-acryloxyl ethyl) ester (HRE)–bonded silica (HRE@SiO 2 ) is developed to separate and purify PTX from crude yew-bark extract using high-performance liquid chromatography. In HRE@SiO 2 , HRE molecules, which are functional ligands, are bonded to the surface of a silica gel matrix using a coupling agent, (3-mercaptopropyl)trimethoxysilane. The proposed HRE@SiO 2 stationary phase was characterized by Fourier-transform infrared spectroscopy, elemental analysis, thermogravimetric analysis, scanning electron microscopy, laser diffraction granulometry, and nitrogen gas adsorption. The HRE@SiO 2 column exhibited excellent chromatographic performance, satisfactory performance reproducibility, and typical reversed-phase chromatographic behavior. An HRE@SiO 2 column was used to separate PTX and its analogs, achieving resolutions exceeding 7.43 for consecutively eluted species. Stoichiometric displacement theory for retention (SDT-R), the van Deemter equation, and van 't Hoff plots were used to analyze the separation mechanism and properties of the HRE@SiO 2 column. The results showed that hydrophobic interactions determine the analyte retention and the separation of PTX and its analogs on an HRE@SiO 2 column is an exothermic process driven by enthalpy. Furthermore, an HRE@SiO 2 column was employed to separate and purify PTX from crude yew-bark extract, increasing PTX purity from 6% to 82%. The findings of this study provide insights for developing rosin-based stationary phases for the separation of natural products.
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高影响因子
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