PLANT AND CELL PHYSIOLOGY
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2017
·Vol. 58
·期 11
·1878-1890
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IF 4.76
Hao Juan,Guo Hong,Shi Xinai,Wang Ye,Wan Qinghua,Song Yao-Bin,Zhang Lei,Dong Ming,Shen Chenjia
Taxus species are well-known for paclitaxel, which exhibits antitumor activities and is used for treating various cancers. Although most Taxus species are widespread in many areas, few studies have characterized the variation in metabolism among different Taxus species. Using an integrated approach involving ‘tandem mass tag’ labeling and liquid chromatography–tandem mass spectrometry (HPLC–MS), proteomes of T. media and T. mairei were investigated and 4078 proteins were quantified. Screening and classification of differentially expressed proteins revealed many metabolism-associated proteins. In detail, four enzymes involved in the flavonoid biosynthesis pathway were predominantly expressed in T. mairei. Four enzymes associated with supplying precursors for paclitaxel biosynthesis and three cytochrome P450 taxoid oxygenases were preferentially expressed in T. media compared with T. mairei. Furthermore, variations in taxoid contents between T. media and T. mairei were determined using HPLC–MS analysis. Variations in flavonoid contents between T. media and T. mairei were determined by HPLC analysis. A number of differentially expressed proteins may provide an explanation for the variation in metabolisms of different Taxus species.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Jia Fu,Wei Zhao,Na Liang,Shaoping Sun
The treatment outcomes of chemotherapy are far from satisfactory due to suboptimal cellular uptake and inadequate intracellular release of antitumor drugs. Meanwhile, M2-like tumor associated macrophages (TAMs) in the tumor microenvironment promote cancer growth and metastasis. The combined strategy of chemotherapy and reprogramming M2-like TAMs within tumor microenvironment has emerged as a novel paradigm for cancer therapy. Hence, a pH-sensitive double-targeted inclusion complex was constructed for combined cancer therapy through the controlled paclitaxel (PTX) delivery and re-education of M2-like TAMs. The inclusion complex employed arginine and biotin modified hydroxypropyl-β-cyclodextrin (Arg-CD-Bio) as the host, with benzimidazole and mannose modified hyaluronic acid (BM-HA-Man) as the pH-sensitive plug. PTX was encapsulated in the inclusion complex. In vitro experiments indicated that the Arg-CD-Bio/BM-HA-Man inclusion complex could facilitate the specific release of PTX at the tumor site. The inclusion complex could be effectively internalized by M2-like TAMs and MCF-7 cells and further reprogramme M2-like TAMs to M1-like TAMs. In vivo antitumor therapy in 4T1 tumor-bearing mice had achieved remarkable suppression efficacy. These results suggested that the PTX-loaded Arg-CD-Bio/BM-HA-Man inclusion complex was a promising platform for efficient cancer treatment.
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MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Wenliang Sun,Chao Han,Ruirui Ge,Xiaotong Jiang,Yu Wang,Yingchao Han,Ning Wang,Yanzhi Song,Mingshi Yang,Guoliang Chen,Yihui Deng
Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand–receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
·
IF 3.65
Zhi-qiang Yuan,Ji-zhao Li,Yang Liu,Wei-liang Chen,Shu-di Yang,Chun-ge Zhang,Wen-jing Zhu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
This study aimed to prepare efficient cRGDyK peptide-decorated micelles for the targeted therapy of non-small-cell lung cancer (NSCLC). An amphiphilic copolymer N -succinyl-palmitoyl-chitosan (SPCS) was synthesized and characterized. cRGDyK peptide is a ligand that can target tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. cRGDyK-functionalized SPCS micelles loaded with paclitaxel (PTX/cRGDyK-SPCS) were prepared by film dispersion method and then characterized according to morphology, size, and zeta potential . PTX/cRGDyK-SPCS micelles presented pH-triggered drug release behavior under acidic conditions. The accumulation of micelles detected by laser confocal fluorescence microscopy and flow cytometry showed that cRGDyK-SPCS micelles were easily taken up by A549 cells marked with the luciferase gene (luc-A549). Meanwhile, co-localization of the micelles and lysosomes was recorded dynamically using a live cell station. MTT assays and cell apoptosis studies revealed that cell viability was significantly inhibited by PTX/cRGDyK-SPCS micelles. More importantly, in vivo animal studies showed that cRGDyK-SPCS micelles mainly accumulated in the orthotopic tumor site. PTX/cRGDyK-SPCS micelles exhibited better anti-tumor activity in subcutaneous and orthotopic lung tumors compared with PTX/SPCS micelles and Taxol ® . These results suggested that PTX/cRGDyK-SPCS micelles had better cancer targeting capacity and superior anti-tumor efficacy. Thus, these micelles have great potential as novel carriers in delivering anti-tumor drugs.
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RSC Advances
·
2016
·Vol. 6
·期 103
·100765-100771
·
IF 3.289
Chang Shu,Eboka Majolene B. Sabi-mouka,Wen Yang,Zhongyang Li,Li Ding
In this work, we designed a self-assembly peptide hydrogel encapsulated paclitaxel (PTX) and suberoylanilide hydroxamic acid (SAHA) for cancer co-delivery (Nap–PTX–SAHA). The hydrogels exhibited uniform nanofibers that entangle to form stable networks and pore microstructures (about 140–180 nm) resulting in absorption and storage of hydrophobic drugs. The circular dichroism (CD) spectra of hydrogels exhibit β-turn-like features. Nap–PTX–SAHA hydrogels achieved control over different types of drugs loading and released by diffusion and relaxation processes. Hydrogels exhibited better therapeutic effect and greater synergetic effect compared to the free drugs in vitro and in vivo. Injection of the hydrogels appears to achieve long-term drug release with higher efficacy and better biocompatibility than free drugs. As for the drug biodistribution studies in tumor-bearing mice, the PTX and SAHA from Nap–PTX–SAHA gels uptake in liver, lung and tumor were more than that of free PTX and SAHA. In comparison with free PTX or SAHA, the Nap–PTX–SAHA gels lower the uptake of released drug significantly in the heart, spleen, and kidney to reduce the cardiotoxicity and renaltoxicity. In conclusion, the Nap–PTX–SAHA gels certainly reduce the side effects of PTX and SAHA, enhance synergistic anticancer effects and suppress the drug resistance of PTX. This strategy can be a basis for designing appropriate clinical trials and will hold promise in nanomedicine for different drug combinations.
研究领域:
药学
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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
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生物医学工程
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PHYTOMEDICINE
·
2026
·
IF 11.3
Huihui Shi,Feifei Li,Meng Wang,Mengyue Zhu,Bei Deng,Dongpo Li,Yuming Yao,Meiling Zhou
The FA-modified pH-sensitive micelles (FA-PM@QCT/PTX) can enhance tumor targeting and lysosome-triggered drug release. • The system reverses chemotherapy resistance via the synergistic action of co‑delivered quercetin and paclitaxel, significantly enhancing cytotoxicity and inducing apoptosis in drug‑resistant cancer cells. • The system demonstrates potent antitumor efficacy with excellent biocompatibility in vivo , markedly inhibiting tumor growth while showing minimal systemic toxicity. Background Chemotherapy remains a major challenge in the effective treatment of non-small cell lung cancer (NSCLC), particularly due to chemotherapy resistance. Natural products, including Chinese herbal extracts, have shown potential for improving chemotherapy sensitivity, but their clinical application is limited by poor tumor targeting and insufficient in vivo stability. Purpose This study aimed to improve PTX-based treatment against resistant NSCLC by developing a FA receptor-targeted pH-sensitive co-delivery system for QCT and PTX. Study design A novel FA receptor-targeted pH-responsive nano-delivery system, FA-PM@QCT/PTX, was constructed and evaluated using PTX-resistant A549/Taxol cells and A549/Taxol tumor-bearing mouse models. Methods FA-PM@QCT/PTX was prepared and characterized in terms of particle size, PDI, zeta potential, encapsulation efficiency, and drug-loading content. In vitro pH-responsive release, cellular uptake, QCT/PTX synergism, cytotoxicity, apoptosis, cell-cycle distribution, P-gp expression, PI3K/Akt signaling, apoptosis-related proteins, and intracellular PTX retention were evaluated in A549/Taxol cells. Pharmacokinetics, tissue distribution, antitumor efficacy, survival benefit, and preliminary systemic safety were further assessed in A549/Taxol tumor-bearing mice. Results FA-PM@QCT/PTX showed a particle size of 166.75 ± 4.10 nm, a PDI of 0.14 ± 0.03, and a zeta potential of -6.34 ± 0.52 mV. The encapsulation efficiencies were 82.48 ± 3.82% for QCT and 84.17 ± 1.21% for PTX, with drug-loading contents of 3.64 ± 0.17% and 3.59 ± 0.11%, respectively. The self-assembled micelles could be internalized by tumor cells via FA receptor-mediated uptake and promote drug release under acidic lysosomal conditions. Chou-Talalay analysis showed that QCT enhanced the inhibitory effect of PTX on A549/Taxol cells, and the actual PTX:QCT molar ratio in FA-PM@QCT/PTX was approximately 1:3, which remained synergistic with a combination index (CI) value of 0.927 ± 0.021. Mechanistically, FA-PM@QCT/PTX reduced P-gp expression, enhanced intracellular PTX retention, suppressed PI3K/Akt signaling, and promoted apoptosis-related pathway activation. In vivo , FA-PM@QCT/PTX improved tumor drug accumulation and prolonged the median survival of A549/Taxol tumor-bearing mice to 52 days without obvious systemic toxicity. Conclusions These results suggest that FA-PM@QCT/PTX may provide a promising co-delivery strategy for improving PTX-based treatment against resistant NSCLC. Download: Download high-res image (371KB) Download: Download full-size image
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DRUG METABOLISM AND DISPOSITION
·
2026
·
IF 3.6
Jiayi Yao,Jiaqi Wang,Peipei Bu,Kexin Liu,Mingyang Zhao,Jingkai Gu,Xiangjun Meng
Fluorescent probes are extensively used for tracking the in vivo behavior of nanocarriers. However, the impact of fluorescent probes on the in vivo fate of nanomedicines remains uncertain. Potential interference from the probes may lead to misleading conclusions. This study investigated the influence of a commonly used fluorescent probe, DiI, on the in vivo fate of paclitaxel (PTX)-loaded polymeric micelles (PMs) in rats. The drug release kinetics of PTX-loaded PMs (PTX-PM) with DiI/PTX co-loaded PMs (DiI/PTX-PM) in rat plasma was quantitatively compared. The results indicate that co-encapsulation with DiI significantly exacerbated drug release and altered the protein binding of PTX through competitive binding, resulting in an increased proportion of free PTX. DiI enhanced diffusion-driven drug leakage without affecting the micelle dissociation kinetics. Notably, DiI inhibited elimination and increased the systemic exposure of both the free micelle material and the nanocarrier. This study provides evidence that DiI can potentially interfere with the in vivo fate of both the therapeutic payload and the nanocarrier, highlighting the necessity for rigorous validation when employing it for nanocarrier tracking.
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RSC Advances
·
2016
·Vol. 6
·期 28
·23693-23701
·
IF 3.289
Jiulong Zhang,Kang Chen,Ying Ding,Xiu Xin,Wenpan Li,Mengjun Zhang,Haiyang Hu,Mingxi Qiao,Xiuli Zhao,Dawei Chen
pH-Sensitive copolymers have been widely used in drug delivery systems to selectively enhance drug release at tumor sites. Herein, dextran (DX) was conjugated with poly(lactide-co-glycolide) (PLGA) and histidine (His) to prepare a pH-responsive nanocarrier, dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) micelles, for the delivery of antitumor drugs. Different grafting ratio HDP micelles were synthesized and prepared successfully and confirmed by the critical micelle concentration (CMC) and particle size distribution (PSD). In vitro drug release showed that the release behaviour of paclitaxel (PTX) loaded HDP micelles was pH-dependent. All blank micelles were nontoxic in the in vitro cytotoxicity assay. In an MTT assay, PTX-loaded HDP micelles with medium grafting ratios (MHDP) showed the highest cytotoxicity against MCF-7 cells. Cellular uptake experiments revealed that these pH-sensitive micelles could be taken up effectively and PTX could be delivered into the cytoplasm to reach the antitumor effect. NIR fluorescence imaging experiments demonstrated that HDP micelles could specifically accumulate in tumor sites via enhancing the permeability and retention (EPR) effect to reduce their systematic toxicity. In vivo antitumor activities showed that HDP micelles could effectively inhibit tumor growth and prolong survival time compared with free PTX solution. These results confirm that the biocompatible pH-responsive HDP micelles are a novel nanocarrier for the intracellular delivery of PTX.
研究领域:
药剂学
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高分子化学
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癌症研究
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药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Qiu-yue Wang,Yali-Xiang,Qiu-hui Hu,Shuang-hui Huang,Juan Lin,Qing-han Zhou
Recently, the stimulus-sensitive drug co-delivery system has gained increasing attentions in the clinic and exhibits improved efficiency rather than the mono-chemotherapy in anti-tumor therapy. Herein, the smart charge switchable nano-micelles (NMs) were fabricated for the endosomal escape mediated co-delivery of doxorubicin (DOX) and paclitaxel (PTX) in treatment of lung adenocarcinoma. The disulfide bonds were facilitated as the linker of the polymer backbone to achieve the redox-sensitive degradation by high intracellular GSH, and acid-liable DMMA was grafted onto DOX molecules for pH-triggered drug release under acidic tumoral microenvironment. Folic acid (FA) was utilized as targeting molecule for facilitating entry of the as prepared NMs into cancer cells. Remarkably, the as fabricated NMs exhibited surface charge-switch from negative to positive during transmitting from physiological pH to the tumor extracellular pH, which can improve the cellular internalization towards cancer cell. Subsequently, the “proton-sponge” effect mediated endosome escape of the NMs was facilitated in the acidic endo/lysosome environment. By the cell assay , the NMs possessed good biocompatibility, excellent cellular uptake, and improved inhibition rate against cancer cell. Moreover, the co-delivery of DOX/PTX exhibited synergistic and enhanced solid tumor inhibition efficiency comparing to mono-chemotherapy in A-549 tumor bearing mice model. Based on above experimental results, the as prepared drug co-delivery system showed promising biosafety and potentials for efficient lung adenocarcinoma treatment in clinic.
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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生物医学工程
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高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Hang Chen,Sifan Huang,Heyi Wang,Xinmei Chen,Haiyan Zhang,Youfa Xu,Wei Fan,Yun Pan,Qiuyan Wen,Zhizhe Lin,Xuena Wang,Yongwei Gu,Baoyue Ding,Jianming Chen,Xin Wu
Background Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives.Methods In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA).Results Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles.Conclusions This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.
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Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-34
·
IF 5.7
Tan Tiantian,Feng Yuxin,Wang Weimin,Wang Rongrong,Yin Liyan,Zeng Yiying,Zeng Zhaowu,Xie Tian
Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.
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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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