DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Xin-Cheng Zhong,Wen-Hong Xu,Zi-Ting Wang,Wang-Wei Guo,Jie-Jian Chen,Ning-Ning Guo,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi-Ying Lu,Qi-Yao Yang,Min Han,Dong-Hang Xu,Jian-Qing Gao
Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor.Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR.Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo.Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs.Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 21
·3970-3981
·
IF 4.543
Mengjun Zhang,Shasha Jing,Jie Zhang,Jiulong Zhang,Xinlong Zang,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Dawei Chen
Multidrug resistance (MDR) has been a major obstacle to tumor chemotherapy. Pluronic unimers have been reported to be promising copolymers to reverse MDR, and the intracellular delivery of Pluronic unimers is a problem worth thinking. To exert the excellent reversal effect of Pluronic unimers, DOX-loaded G4.0 PAMAM was modified with PluronicL64 via cis-aconitic acid as a pH-sensitive linkage (PCPAMAM/DOX), which could release DOX and Pluronic unimers into cytoplasm. The Pluronic-modified PAMAM (PCPAMAM) exhibited favorable biocompatibility and pH-sensitivity. PCPAMAM/DOX showed a nano-scale size and a sustained in vitro release profile. Compared with a control formulation, PCPAMAM/DOX showed a higher reversal effect on MCF-7/ADR cells and enhanced intracellular drug accumulation. The results of P-gp activity, subcellular distribution of PluronicL64, the ATP level and mitochondrial transmembrane potential all illustrated that free Pluronic unimers could be released by PCPAMAM functioning as reversal agents. In conclusion, PCPAMAM could be a promising vehicle to enhance DOX accumulation by overcoming MDR in MCF-7/ADR cells. This work also provided an effective method to deliver Pluronic unimers into MDR cells.
研究领域:
药剂学
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癌症研究
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2016
·Vol. 34
·期 3
·610-618
·
IF 3.26
Chao Yanhui,Liang Yuheng,Fang Guihua,He Haibing,Yao Qing,Xu Hang,Chen Yinrong,Tang Xing
Purpose DOX is one of the most potent anticancer drugs. But its short half-life and the occurrence of multi-drug resistance (MDR) markedly limit its clinical application. To solve these problems, we develop DOX loaded polymersomes (DOX polymersomes). Methods An methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-b-PCL) copolymer was synthesized and used to prepare DOX polymersomes. The pharmaceutical properties of DOX polymersomes were characterized. The in vitro release profile of DOX from polymersomes was investigated. The in vitro cytotoxicity and cell uptake studies were performed on MCF-7 and MCF-7/ADR cells. The in vivo pharmacokinetic profiles were investigated on Sprague–Dawley rats. Results DOX polymersomes had a nano-scale particle size of about 60 nm with a hydrophobic membrane about 10 nm in thickness. Release of DOX from the polymersomes took place in a sustained manner. Cell experiments showed DOX polymersomes enhanced the cytotoxicity and the intracellular accumulation of DOX in MCF-7/ADR cells, compared with free DOX. In vivo pharmacokinetic study showed the DOX polymersomes increased the bioavailability and prolonged the circulation time in rats. Conclusions The entrapment of DOX in biodegradable polymersomes could enhance cytotoxicity in MCF-7/ADR cells and improve its in vivo pharmacokinetic profile.
研究领域:
药剂学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 19
·3531-3540
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IF 4.543
Hao Zhu,Yun Wang,Abid Hussain,Zhipeng Zhang,Yuanyuan Shen,Shengrong Guo
Co-delivery of two or more chemotherapeutic agents via nanocarriers can provide an effective approach to maximize synergistic or additive effects. In this work, we developed novel nanodiamond (ND) based nanoparticle co-loading of doxorubicin (DOX) and malaridine (MAL) for treatment of MCF-7/ADR cells by virtue of the good biocompatibility, high drug loading capacity and pH-responsive drug release properties of NDs. The combination index (CI) was the smallest, 0.17, for DOX and MAL against MCF-7/ADR cells, when their ratio was 5 : 1, showing the greatest synergistic effects. (DOX + MAL)@NDs or FA-PEG–DOX/(DOX + MAL)@NDs with different ratios of DOX to MAL (4 : 1, 5 : 1 and 6 : 1) were prepared by simple physical adsorption of DOX, MAL and FA-PEG–DOX. Among them, (DOX + MAL)@NDs with the mass ratio of 5 : 1 had the smallest CI of 0.08. The concentrations of DOX and MAL for (DOX + MAL)@NDs producing 50% growth inhibition were 1.90 and 0.35 μg mL−1, respectively, smaller than the 50% inhibitory concentrations for DOX@NDs and MAL@NDs (10.75 and 4.38 μg mL−1) and for free DOX and free MAL (49.65 and 9.03 μg mL−1). (DOX + MAL)@NDs were not stable in water, FA-PEG–DOX/(DOX + MAL)@NDs could stay stable in water for 24 h due to steric repulsion effects offered by PEG, which also compromised their cytotoxicities to some extent. (DOX + MAL)@NDs or FA-PEG–DOX/(DOX + MAL)@NDs presented faster DOX and MAL co-release at pH 5.5 than 7.4. The high anti-tumor efficacy suggested that the ND mediated DOX and MAL co-delivery system could be promising for the treatment of multi-drug resistant cancer.
研究领域:
药理学
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纳米技术
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
XENOBIOTICA
·
2016
·
IF 1.723
Rui-Ping Ye,Zhen-Dong Chen
1. The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multidrug resistance (MDR). Saikosaponin A (SSA) is a triterpenoid saponin isolated from Radix Bupleuri. This study was mainly designed to understand effects of SSA on MDR in MCF-7/ADR and HepG2/ADM cells.2. MDR reversal was examined as the alteration of cytotoxic drugs IC50 in resistant cells in the presence of SSA by MTT assay, and was compared with the non-resistant cells. Apoptosis and uptake of P-gp substrates in the tumor cells were detected by flow cytometry. Western blot was performed to assay the expression of P-gp.3. Our results demonstrate SSA could increase the chemosensitivity of P-gp overexpressing HepG2/ADM and MCF-7/ADR cells to doxorubicin (DOX), vincristine (VCR) and paclitaxel. SSA promoted apoptosis of MCF-7/ADR cells in the presence of DOX. Moreover, it could also increase the retention of P-gp substrates DOX and rhodamine 123 in MCF-7/ADR cells, and decrease digoxin efflux ratio in Caco-2 cell monolayer. Finally, a mechanistic study showed that SSA reduced P-gp expression without affecting hydrolytic activity of P-gp.4. In conclusion, our findings suggest that SSA could be further developed for sensitizing resistant cancer cells and used as an adjuvant therapy together with anticancer drugs to improve their therapeutic efficacies.
研究领域:
肿瘤学
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药理学
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细胞生物学
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中医药学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2019
·
IF 2.606
Shaohui Xu,Zhu Jin,Zhipeng Zhang,Wei Huang,Yuanyuan Shen,Zhongmin Wang,Shengrong Guo
It is necessary for effective combinational effects that multiple chemotherapeutic agents enter and act on the same tumor cells simultaneously at a suitable ratio. Due to their individual physicochemical or biopharmaceutical properties, they cannot reach the same cells at its predetermined ratio after co-administration. Herein, we report a novel system with precise ratiometric co-loading, co-delivery and intracellular co-release of paclitaxel (PTX) and curcumin (CUR), to investigate their synergistic effects. We prepared the system by conjugating PTX and CUR at different ratios onto the same gold nanorods (GNRs). We demonstrated that PTX and CUR could be precisely ratiometric co-loaded to form dual-drug conjugated biotin-PEG modified GNRs (abbreviated as PTX/ [email protected] ), which could co-deliver dual drugs into tumor cells with a predetermined ratio and co-release them intracellularly. The PTX/ [email protected] with the mass ratio of PTX and CUR at 1:1 exhibited the best synergistic effect on multidrug resistant MCF-7/ADR cells while the free PTX and CUR mixture with the mass ratio of at 1:0.75 displayed the strongest synergism. Cytotoxicity studies showed that PTX/ [email protected] are superior to free drug mixture. Furthermore, PTX/ [email protected] could remarkably induce apoptosis of MCF-7/ADR cells under near-infrared irradiation. Moreover, we found that PTX/ [email protected] significantly inhibited P-glycoprotein (P-gp) expression in MCF-7/ADR cells.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
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2018
·
IF 3.095
Qingqing Huang,Tiange Cai,Qianwen Li,Yinghong Huang,Qian Liu,Bingyue Wang,Xi Xia,Qi Wang,John C. C. Whitney,Susan P. C. Cole,Yu Cai
Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer–lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer–lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STEROIDS
·
2017
·
IF 2.282
Xiao-Long He,Yajing Xing,Xiang-Zhong Gu,Jie-Xin Xiao,Ying-Ying Wang,Zhengfang Yi,Wen-Wei Qiu
In this paper, a new and concise synthetic route of lithocholic acid (LCA) using commercially available steroid source deoxycholic acid is reported. A series of amide derivatives of LCA were also synthesized and investigated for their activity against the growth of MCF-7 and MCF-7/ADR cells using the sulforhodamine B assay. For MCF-7, the most potent compound 20 showed a 20-fold higher antitumor activity than LCA. For MCF-7/ADR, the most potent compound 24 showed a 22-fold higher antitumor activity than LCA. The transwell migration assay of 20 was evaluated on MDA-MB-231 cells. The colony formation and apoptosis assays of 20 were performed on MCF-7 and MCF-7/ADR cell lines.
研究领域:
药理学
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有机合成化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2020
·Vol. 5
·期 4
·2001047
·
IF 12.13
Jianqiao Chang,Yu Zhang,Yike Li,Ziwei Han,Fei Tian,Chao Liu,Qiang Feng,Yuguang Wang,Jiashu Sun,Lu Zhang
Detection of mRNA expression in live cells during treatment is a challenging task, despite its importance in tumor biology and potential therapeutic leads. Here a multilayer ratiometric fluorescent nanomachine for live-cell perturbation and imaging of mRNA at single cell resolution is reported. The nanomachines fabricated by microfluidic approaches consist of fluorescent polymeric cores and multiple lipid layers, which can efficiently deliver siRNA and molecular beacons (MBs) to cytosol and then release the cargo in a sequential way. The siRNA molecules released from the outer lipid layers lead to silencing of multidrug resistance 1 (MDR1) gene, and the MBs from the middle lipid layers detect the presence of MDR1 mRNA. The fluorescent ratio of MBs to fluorescent polymeric cores positively correlates with the expression level of MDR1 mRNA in MCF-7/ADR cells during siRNA treatment. The nanomachines provide comparable results with traditional qPCR for quantifying mRNA, showing great potential for modulation and imaging of intratumoral mRNA in vitro and in vivo.
研究领域:
生物技术
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分子生物学
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癌症研究
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Xiu-Qing Song,Lin-Lin Tian,Tao Ye,Hu Liu,Hua Zhang
ABSTRACT Twenty compounds comprising four pregnane steroids ( 2 – 4 & 20 ) and 16 pregnane glycosides ( 1 & 5 – 19 ) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima . Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones ( 1 – 17 ) being reported for the first time, including the rare cases ( 2 & 3 ) of free C 21 steroids with 17α-acetyl substitution, compounds 4 – 7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution ( 7 ) and glycosylation at C-12 position ( 10 & 11 ). An empirical rule for the identification of C-17 configuration, in C 21 steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.
研究领域:
药理学
·
化学
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民族药理学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 7
·期 6
·974-985
·
IF 4.776
Abid Hussain,Shengrong Guo
To prevent premature drug release from nanoparticles, it is vital to design and prepare controlled and site-specific drug release systems. We investigated a new controllable drug release mesoporous carbon nanoparticle (MCN)-based nano-system with the advantages of enhanced permeability and retention effect (EPR) to target tumors followed by the NIR-induced heat-triggered release of a chemotherapeutic drug to show anti-tumor effects. The pores of MCN with photo-thermal effects were filled with the chemotherapeutic agent doxorubicin (DOX) and the phase change material (PCM) 1-tetradecanol was used as a gatekeeper to trap DOX inside the pores of the mesoporous carbon nanoparticles and the release of DOX inside tumor cells was triggered using NIR irradiation. The surface of MCN was coated with natural sophorolipid (SLPD) to obtain nanoparticles (DOX-PCM@MCN-SLPD) with good biocompatibility, dispersibility and stability in aqueous solutions. The MCN-based nano-system had the ability to load 24% DOX trapped with the PCM before coating with SLPD. It was observed that the release of DOX was temperature-dependent above the melting point of PCM. Once DOXPCM@MCN-SLPD was delivered into MCF-7/ADR cells, the release of DOX was triggered by MCN-borne photo-thermal effects under NIR irradiation. The amount of DOX inside the tumor was visualized via confocal laser scanning microscopy, which showed a higher amount of DOX at a higher temperature compared to that at normal body temperature, further confirming the minimization of premature drug release at 37 °C.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Chen Zhenzhen,Liu Zhihong,Zhang Qian,Huang Sheng,Zhang Zaizhong,Feng Xianquan,Zeng Lingjun,Lin Ding,Wang Lie,Song Hongtao
Drug resistance is a huge hurdle in tumor therapy. Tumor hypoxia contributes to chemotherapy resistance by inducing the hypoxia-inducible factor-1α (HIF-1α) pathway. To reduce tumor hypoxia, novel approaches have been devised, providing significant importance to reverse therapeutic resistance and improve the effectiveness of antitumor therapies. Herein, the nanosystem of bovine serum albumin (BSA)-templated manganese dioxide (MnO2) nanoparticles (BSA/MnO2 NPs) loaded with doxorubicin (DOX) (DOX-BSA/MnO2 NPs) developed in our previous report was further explored for their physicochemical properties and capacity to reverse DOX resistance because of their excellent photothermal and tumor microenvironment (TME) response effects. The DOX-BSA/MnO2 NPs showed good biocompatibility and hemocompatibility. Meanwhile, DOX-BSA/MnO2 NPs could greatly affect DOX pharmacokinetic properties, with prolonged circulation time and reduced cardiotoxicity, besides enhancing accumulation at tumor sites. DOX-BSA/MnO2 NPs can interact with H2O2 and H+ in TME to form oxygen and exhibit excellent photothermal effect to further alleviate hypoxia due to MnO2, reversing DOX resistance by down-regulating HIF-1α expression and significantly improving the antitumor efficiency in DOX-resistant human breast carcinoma cell line (MCF-7/ADR) tumor model. The hypoxia-ameliorated photothermal MnO2 platform is a promising strategy for revering DOX resistance.
研究领域:
癌症治疗
·
纳米技术
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）