JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
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2026
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IF 1.8
Zhenhe Huang,Yumei Qiu,Fangchu Liu,Xiaoli Chen,Xintao Wang
ObjectiveTo investigate whether naringin enhances the chemosensitivity of nasopharyngeal carcinoma–derived CNE2 cells to paclitaxel and identify potential molecular mediators.MethodsCNE2 cells were treated with naringin alone or in combination with paclitaxel, cisplatin, or 5-fluorouracil. Cell viability, proliferation, and migration were assessed using cell counting kit-8 and Transwell assays. Transcriptomic profiling followed by bioinformatic analysis of Gene Expression Omnibus datasets (GSE53819, GSE12452, and GSE102349) was performed to identify nasopharyngeal carcinoma prognosis–related genes. AKR1C3 overexpression was established via lentiviral transduction, and pharmacological inhibition was performed using ASP9521. mRNA and protein expression were validated using reverse transcription quantitative polymerase chain reaction and Western blot analysis.ResultsNaringin (160 μM) demonstrated a trend toward reducing the half-maximal inhibitory concentration of paclitaxel from 10.52 to 8.04 nM; however, it did not significantly alter sensitivity to cisplatin or 5-fluorouracil. Combined treatment with 2 nM paclitaxel and 160 μM naringin synergistically suppressed CNE2 proliferation and migration compared with that using either agent alone (p < 0.05). Bioinformatic analysis revealed that high AKR1C3 expression was correlated with improved survival in patients with nasopharyngeal carcinoma (p < 0.05), whereas high PAIP1, PRKDC, PTPRR, and COL12A1 expressions were correlated with poorer outcomes. Reverse transcription quantitative polymerase chain reaction confirmed that both naringin and paclitaxel upregulated AKR1C3 mRNA, with the combination producing the strongest effect. Gain-of-function studies demonstrated that AKR1C3 overexpression significantly enhanced paclitaxel sensitivity, with half-maximal inhibitory concentration values decreasing from 13.63 to 6.994 nM in CNE2 cells and from 8.534 to 4.668 nM in CNE1 cells. Furthermore, the specific AKR1C3 inhibitor, ASP9521, significantly attenuated the synergistic anti-proliferative and anti-migratory effects of paclitaxel + naringin in CNE2 cells, confirming that naringin enhances chemosensitivity to paclitaxel by upregulating AKR1C3 expression.ConclusionsNaringin sensitizes CNE2 cells to paclitaxel, potentially via AKR1C3 upregulation. This flavonoid may represent a low-toxicity adjunct to enhance the efficacy of paclitaxel in nasopharyngeal carcinoma.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Congcong Lin,Jiamin Sun,Yun Yang,Xinyao Pan,Shiyu Wang,Xiaoyang Li,Yan Zhang,Huile Gao,Chunli Gan
The development of chemotherapy resistance poses a major challenge in cancer therapy. Ferroptosis, a unique type of cell death, offers a promising strategy to combat this resistance. Herein, a peptide-based nanoassembly (PTX@CPG) consisting of paclitaxel (PTX), chlorin e6 (Ce6), and FFVLKPLGLAGK-(PEG8) 3 was constructed to promote ferroptosis through reactive oxygen species (ROS) accumulation and overcome chemoresistance. Specifically, the small-sized PTX@CPG nanoparticles effectively penetrate tumors, where the microenvironment-responsive peptide is selectively cleaved by the high expression of matrix metalloproteinase 2. This process facilitates the targeted release of PTX and its reassembly into nanofibers, improving the tumor retention of Ce6 and enhancing its cellular uptake. The synergistic therapeutic effects of PTX in combination with photodynamic therapy on triple-negative breast cancer cells were validated through both in vitro and in vivo experiments. Impressively, upon laser irradiation, PTX@CPG significantly increased ROS production, thereby amplifying the ferroptosis-inducing effects of PTX. Moreover, ferroptosis triggered by PTX@CPG with laser reduced the levels of P-glycoprotein and glutathione peroxidase 4, contributing to the alleviation of chemoresistance. Overall, PTX@CPG with laser demonstrated effective spatial targeting and drug retention, enhancing ferroptosis through ROS accumulation and showcasing a promising approach for overcoming chemotherapy resistance in cancer therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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PubMed
高影响因子
Journal of Neuroinflammation
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2026
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IF 11.5
Xiaojing Liu,Meng Zhang,Yue Zhang,Yining Hao,Dayun Lu,Wenjun Li,Xu Shen
Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a severe side effect lacking effective treatment, largely due to its complex and poorly understood pathogenesis. Here, we observed the pathological inhibition of phosphatase PPM1A activity in the dorsal root ganglia (DRG) tissues of PIPN mice. We also found that otilonium bromide (OB), as a PPM1A activator, ameliorated the PIPN-like pathology in mice, as evidenced by the alleviation of sensory dysfunction, myelin sheath injury, intraepidermal nerve fiber loss and vascular lesions. Using PPM1A-specific knockdown mice, we demonstrated that OB suppresses pro-inflammatory M1 macrophage polarization in the DRG through the PPM1A/NF-κB/NLRP3/IL-1β pathway, thereby alleviating axonal degeneration and neuronal apoptosis. In vitro experiments revealed that PTX-damaged DRG neurons release high-mobility group box 1 (HMGB1) to promote pro-inflammatory macrophage polarization, while OB disrupts this neuron-macrophage interaction by limiting HMGB1 release and subsequent macrophage activation. Together, our findings highlight PPM1A activation as a promising therapeutic strategy for PIPN and identify OB as a potential agent for treating this clinical side effect.
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Jianhao Xu,Cunjin Su,Fenglun Zhao,Jialong Tao,Duanmin Hu,Aiming Shi,Jie Pan,Yusong Zhang
Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The long-chain non-coding RNA maternally expressed gene 3 (MEG3) is a recognized tumor suppressor . This study aimed to explore the effects of PTX on the expression of MEG3 and its anti-tumor mechanism in lung cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine cell proliferation . Quantitative polymerase chain reaction was used to determine the levels of MEG3 expressions. Western blot and immunofluorescence were used to detect protein levels. Small interfering RNA or pCDNA-MEG3 transfection was used to downregulate or upregulate MEG3 expression. Dichlorof luorescein diacetate was used to detect intracellular reactive oxygen species. Flow cytometry was used to analyze apoptosis. PTX significantly inhibited the proliferation of NSCLC cells and increased the expressions of MEG3 and P53. The downregulation of MEG3 attenuated PTX-induced cytotoxicity, whereas upregulation of MEG3 induced cell death and increased P53 expression. The inhibition of P53 caused no effect on the upstream MEG3 expression. Our results suggest that the MEG3-P53 pathway is involved in the apoptosis of A549 cells induced by PTX.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2013
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IF 3.554
Yan Wang,Shurong Ma,Zhongshi Xie,Haishan Zhang
Doxorubicin was chemically conjugated to a biodegradable polymeric carrier as a polymer-doxorubicin (polymer-Dox) conjugate via an acid labile Schiff-base bond. Then, paclitaxel was physically encapsulated by the polymer-Dox conjugate to self assemble in water as micellar nanoparticles with both doxorubicin and paclitaxel in one nanoparticle. In this way, doxorubicin and paclitaxel were combined. The preparation of the polymer-doxorubicin conjugates, encapsulation of paclitaxel, characterization of nanoparticles was systematically studied and the biological evaluation of the free drug combination as well as the micellar platform combination in vitro was thoroughly detailed.
研究领域:
药剂学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
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2023
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IF 4.3
Chen Jia-Wei,Shen Yi,Yu Qing-Song,Gan Zhi-Hua
Nanotheranostics, which combine the therapeutic and diagnostic functions in one integrated system, have received extensive attentions in cancer treatments because they enable non-invasive diagnosis, tumor-targeted drug delivery, and real-time monitoring of therapeutic response. However, due to the high systemic toxicity of commonly used chemotherapeutics, current treatment still has limitations. Herein, to simultaneously achieve safe cancer therapy and therapeutic response monitoring, an iodinated prodrug strategy was proposed. 2,3,5-Triiodobenzoic acid (TIBA) was used to modify both paclitaxel (PTX) and the polymeric vehicle, so that the encapsulation efficiency of PTX could be increased and the systemic toxicity could be reduced. As-prepared prodrug nanoparticles could accumulate passively in the tumor site and promptly release loaded drugs in response to the overexpressed GSH in cancer cells, which then caused efficient cell cycle arrest and apoptosis like that of the parent PTX. With this rational design, safe and efficient antitumor therapy and real-time computer tomography (CT) imaging could be simultaneously realized, facilitating potential CT imaging-guided therapy of metastatic breast cancer.
研究领域:
癌症治疗
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纳米技术
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药学
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医学成像
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Shasha Qin,Jiamin Li,Zhiling Pan,Can Wang,Bing-Feng Zhang
Prodrug nanoassemblies fabricated by anticancer drug conjugates exhibited more advantages in controlled drug release and bioavailability and favorable antitumor efficacy. In this paper, lactobionic acid (LA) was connected with polyethylene glycol through amido linkages, and paclitaxel was joined with polyethylene glycol by means of ester bonds to form the prodrug copolymer LA-PEG-PTX. Then, LA-PEG-PTX was automatically assembled into LA-PEG-PTX nanoparticles (LPP NPs) by dialysis. The LPP NPs had a relatively uniform size of approximately 200 nm, a negative potential (−13.68 mV), and a spherical shape under TEM. The drug loading of LPP NPs was 3.91%, which was measured by HPLC. The in vitro release profile of LPP NPs exhibited a sustained release feature. The results of the pharmacokinetic test in rats showed that LPP NPs had higher T 1/2 and AUC values than the control group (free PTX) and a prolonged in vivo circulation time, thus increasing the bioavailability of PTX. Remarkably, the LPP NPs were absorbed into HepG2 cells after galactose-directed internalization and enhanced cytotoxicity. Consequently, LPP NPs displayed notable antitumor activity in Kunming mice with H22 hepatocellular carcinoma. Collectively, these findings suggested that paclitaxel prodrug-based self-assembled nanoparticles were a promising alternative for improving the bioavailability and antitumor effect of PTX.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
Ruoning Wang,Mengmeng Yang,Guoyuan Li,Xin Wang,Zhenhai Zhang,Hongzhi Qiao,Jun Chen,Zhipeng Chen,Xiaobin Cui,Junsong Li
Paclitaxel-betulinic acid hybrid nanosuspensions (PTX-BA-NP) with increased anti-breast cancer activity were developed. The resultant nanosuspensions (NP) had a mean particle size of 282.54 ± 5.4 nm, a polydispersity index of approximately 0.242 ± 0.02, a zeta potential of -19.7 ± 0.19 mV and a redispersibility index of 103.3 ± 0.01%. The cumulative dissolution percentage of PTX coarse powder and PTX-BA-NP dried powder at 60 min were 15.4% and 90.8%, respectively. MCF-7 cell-based testing showed that treatment with PTX-BA-NP led to more PTX-BA-NP accumulation in the cytoplasm of breast cancer cells, less cell cycle arrest in the G2-M phase, more cell cycle arrest in the G0-G1 phase, more apoptosis-induced cell death and stronger inhibition of cell migration than paclitaxel nanosuspensions (PTX-NP). Biodistribution studies showed that tumor accumulation levels at 12 h in the PTX-BA-NP group were approximately 2.67- and 2.33-fold higher than the levels in the Taxol® and PTX-NP groups, respectively. In vivo antitumor efficacy demonstrated that PTX-BA-NP exerted the strongest tumor inhibition among the four groups, with a tumor inhibition rate of 47.79 ± 2.28%, followed by PTX-NP (35.05 ± 5.55%), Taxol® (22.67 ± 6.01%) and betulinic acid nanosuspension (BA NP) (14.38 ± 6.02%). These findings indicate that PTX-BA-NP holds great promise for breast cancer therapy.
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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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
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IF 3.649
Longbing Ling,Yawei Du,Muhammad Ismail,Ruiyu He,Yongpeng Hou,Zhenglin Fu,Ying Zhang,Chen Yao,Xinsong Li
In this report, a newly liposomal formulation of paclitaxel (PTX) based on dual paclitaxel succinate glycerophosphorylcholine (Di-PTX-GPC) prodrug was developed. The Di-PTX-GPC prodrug was synthesized by conjugating PTX with GPC through esterification under N,N ′-carbonyldiimidazole (CDI) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalytic system. Di-PTX-GPC liposomes were prepared by thin film method and characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The results indicated that the liposomes have an average diameter of 157.9 nm with well-defined spherical morphology. In vitro drug release studies confirmed that the Di-PTX-GPC liposomes have controlled release profile of PTX at a weakly acidic environment, which formulates them suitable for sustained drug delivery. Additionally, in vitro cellular uptake analysis and cytotoxicity evaluation showed that Di-PTX-GPC liposomes were internalized successfully into tumor cells to induce the apoptosis against MCF-7, HeLa and HepG-2 cells. In vivo pharmacokinetics study revealed that such liposomal formulation of Di-PTX-GPC has longer retention half-life in bloodstream, which subsequently leads to slight accumulate in tumor sites due to enhanced permeability and retention (EPR) effect. More importantly, Di-PTX-GPC liposomes demonstrated good in vivo anticancer activities compared to Taxol with reduced adverse effects. Conclusively, these results suggest that Di-PTX-GPC liposomes could be an effective PTX delivery vehicles in clinical cancer chemotherapy .
研究领域:
药理学
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肿瘤学
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药物递送系统
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PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2020
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IF 7.097
Jiang Yu,Yingli Wang,Shuang Zhou,Jinbo Li,Jiamei Wang,Dongxu Chi,Xue Wang,Guimei Lin,Zhonggui He,Yongjun Wang
The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX- S -DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu 2+ ) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu 2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
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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Frontiers in Bioengineering and Biotechnology
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2023
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IF 5.7
Ge Ruiliang,Ji Yuexin,Ding Yanfei,Huang Chang,He Hua,Yu Deng-Guang
The poor solubility of numerous drugs pose a long-existing challenge to the researchers in the fields of pharmaceutics, bioengineering and biotechnology. Many “top-down” and “bottom-up” nano fabrication methods have been exploited to provide solutions for this issue. In this study, a combination strategy of top-down process (electrospinning) and bottom-up (self-emulsifying) was demonstrated to be useful for enhancing the dissolution of a typical poorly water-soluble anticancer model drug (paclitaxel, PTX). With polyvinylpyrrolidone (PVP K90) as the filament-forming matrix and drug carrier, polyoxyethylene castor oil (PCO) as emulsifier, and triglyceride (TG) as oil phase, Both a single-fluid blending process and a coaxial process were utilized to prepare medicated nanofibers. Scanning electron microscope and transmission electron microscope (TEM) results clearly demonstrated the morphology and inner structures of the nanofibers. The lipid nanoparticles of emulsions after self-emulsification were also assessed through TEM. The encapsulation efficiency (EE) and in vitro dissolution tests demonstrated that the cores-shell nanofibers could provide a better self-emulsifying process int terms of a higher EE and a better drug sustained release profile. Meanwhile, an increase of sheath fluid rate could benefit an even better results, suggesting a clear process-property-performance relationship. The protocols reported here pave anew way for effective oral delivery of poorly water-soluble drug.
研究领域:
药剂学
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生物工程
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生物技术
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PubMed
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DRUG DELIVERY
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2023
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IF 6
Yaqin Tu,Wei Zhang,Guorun Fan,Chenming Zou,Jie Zhang,Nan Wu,Jiahui Ding,Wen Qing Zou,Hongjun Xiao,Songwei Tan
High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.
研究领域:
癌症治疗
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药学科学
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纳米技术
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生物医学工程
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产品关联
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PubMed
高影响因子
危险品化学品经营许可证（带存储）