DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2026
·
IF 2.6
Shuai Xia,Tao Sheng,Jia-Min Li,Bing-Feng Zhang,Ruo-Bin Peng,Ping-Bo Yan
Objective The aim of this research was to design nanostructured lipid carriers (NLCs) co-delivering paclitaxel (PTX) and ubenimex (Uben) to improve the tumor microenvironment (TME) and enhance efficacy against breast cancer.Significance Nanostructured lipid carriers offer unique advantages for co-delivery of anti-tumor drugs, including high drug-loading capacity, controlled-release performance, and facile functionalization. This study developed a NLC co-loaded with PTX and Uben to achieve synergistic therapeutic effects on breast cancer by improving the immunosuppressive TME.Methods Ubenimex was conjugated to vitamin E polyethylene glycol succinate (TPGS) via ester bonds, after which the synthetic conjugate, PTX, and lipid materials were formulated into the nanostructured lipid carrier (PTX/Uben-NLC) by the emulsified solvent evaporation-low-temperature curing method and subsequently characterized and evaluated for improved anti-tumor efficacy.Results The prepared PTX/Uben-NLC was approximately spherical with a negative potential and a particle size of about 161 nm. The formulation demonstrated sustained drug release. Uben exhibited pH-responsive release in the weakly acidic TME and induced immune cell activation and secretion of anti-tumor cytokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12)), while secretion of immunosuppressive cytokines (TGF-β and IL-10) was concurrently inhibited. PTX exerted direct anti-tumor effects on tumor cells. Consequently, the PTX/Uben-NLC alleviated TME immunosuppression and enhanced anti-breast-cancer activity.Conclusion Dual-drug-loaded NLCs alleviated TME immunosuppression to enhance synergistic anti-breast cancer therapy and provided a feasible solution for breast cancer treatment.
✓ 已验证
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2012
·Vol. 129
·期 2
·748-755
·
IF 1.289
Xipan Liu,Dan Pan,Qian Guo,Yanjun Zhao,Zheng Wang
This study designed a photo-crosslinkable poly(ether-anhydride) nanocarrier with folate modification to achieve both biodegradability and active targeting. The nanocarrier consists of a hydrophobic polymer core and a shell of folate and hydrophilic poly(ethylene glycol). Nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to verify the synthesis and relevant intermediate products. The nanocarrier was characterized in terms of morphology and diameter using transmission electron microscopy and dynamic light scattering. The results showed that the size of spherical nanocarriers located within 200–400 nm. The cellular uptake profile of nanocarriers in HeLa cells was examined using fluorescence microscope with the help of a fluorescent molecule and the folate-modified nanocarrier exhibited an enhanced uptake compared to that without modification. The nanocarrier degradation at physiological temperature was investigated gravimetrically and the in vitro release of model drug, paclitaxel (PTX) was examined via the dialysis method. The erosion rate of poly(ether-anhydride) network was controlled by the crosslinking density and the hydrolytic susceptibility; the folate modification slightly slowed the degradation process. The time scale of PTX release perfectly matched with that of nanocarrier erosion; after 6 h more than 50% weight loss of nanocarrier was observed and meanwhile the drug release profile got plateaued, indicating the dominant role of polymer erosion in the release of the active agent from the nanocarriers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
研究领域:
生物医学工程
·
药物递送
·
肿瘤治疗
·
材料科学
·
药剂学
✓ 已验证
DOI
高影响因子
Nano Research
·
2024
·
IF 9.5
Jiang Xiaoqian,Qu Aihua,Xu Xinxin,Kuang Hua,Liu Liqiang,Xu Chuanlai
Paclitaxel (PTX), methotrexate (MTX), and 5-fluorouracil (5-FU) are commonly-used small molecule anti-tumor drugs for breast cancer. Unfortunately, drug resistance occurs with long-term treatment or excessive use, and the high concentrations of PTX, MTX, and 5-FU in patients may lead to side effects with dose-limiting toxicities, such as myelosuppression, hepatotoxicity, and peripheral neuropathy. Therefore, concentration monitoring of PTX, MTX, and 5-FU in clinical treatment is very important. We prepared highly sensitive and specific monoclonal antibodies using several haptens, and established a multiple paper-based sensor utilizing optical signals of gold nanoparticles, which simultaneously detected PTX, MTX, and 5-FU in human plasma or urine with 10 min. A portable scanner for quantitative detection in plasma and urine samples was used, and the calculated limit of detection (cLOD) values were 0.002 and 0.142 µg/mL for PTX, 0.187 and 0.976 ng/mL for MTX, and 0.057 and 0.128 µg/mL for 5-FU, respectively. In the recovery test, the recovery rates and the coefficient of variation were 85.84%–108.81% and 1.23%–8.80%, respectively, indicating the reliability and accuracy of the multiple gold immunochromatographic strip (GIS). In addition, for the determination of collected clinical plasma samples, the correlation between the test data of the multiple GIS and liquid chromatography–tandem mass spectrometry (LC–MS/MS) was good. Therefore, the developed multiple GIS could be applied to the rapid detection of PTX, MTX, and 5-FU in different clinical samples.
研究领域:
医学检验
·
药物分析
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Cell Chemical Biology
·
2024
·
IF 6.6
KeJing Zhang,Juan Wei,SheYu Zhang,Liyan Fei,Lu Guo,Xueying Liu,YiShuai Ji,WenJun Chen,Felipe E. Ciamponi,WeiChang Chen,MengXi Li,Jie Zhai,Ting Fu,Katlin B. Massirer,Yang Yu,Mathieu Lupien,Yong Wei,Cheryl. H. Arrowsmith,Qin Wu,WeiHong Tan
Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. In addition, type I PRMT inhibition synergies with PRMT5 inhibition in suppressing tumor growth of drug-resistant cells through augmenting perturbation of AURKB-mediated mitotic signaling pathway. These findings are fully recapitulated in a patient-derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2018
·
IF 0
Wei Zhuang,Linjiao He,Kai Wang,Bo Ma,Lei Ge,Zhenfu Wang,Jinsha Huang,Jinglan Wu,Qi Zhang,Hanjie Ying
Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
Frontiers in Pharmacology
·
2020
·
IF 4.225
Lv Lingyan,Li Xinrui,Qian Wei,Li Shennan,Jiang Yan,Xiong Yaokun,Xu Jianpei,Lv Wei,Liu Xiaoyan,Chen Yun,Tang Yulin,Xin Hongliang
The serious therapeutic obstacles to glioma treatment include poor penetration across the blood-brain barrier (BBB) and low accumulation of therapeutic drugs at tumor sites. In this study, borneol combined with CGKRK peptide (a ligand of the heparan sulfate which overexpress on the glioma cells) modified paclitaxel prodrug self-assembled redox-responsive nanoparticles (CGKRK-PSNPs) were hypothesized to enhance the BBB penetration ability and active tumor targeting efficiency, respectively. The resulting CGKRK-PSNPs possessed a spherical shape with a small particle size (105.61 ± 1.53 nm) and high drug loading for PTX (54.18 ± 1.13%). The drug release behavior proved that CGKRK-PSNPs were highly sensitive to glutathione (GSH) redox environment. The in vitro cell experiments suggested that CGKRK-PSNPs significantly increased the cellular uptake and cytotoxicity of U87MG cells, meanwhile CGKRK-PSNPs showed the low cytotoxicity against BCEC cells. Combined with borneol, CGKRK-PSNPs exhibited enhanced transportation across in vitro BBB model. In intracranial U87MG glioma-bearing nude mice, the higher accumulation of CGKRK-PSNPs combined with borneol was observed through real-time fluorescence image. Moreover, the in vivo anti-glioma results confirmed that CGKRK-PSNPs combined with borneol could improve the anti-glioma efficacy with the prolonged medium survival time (39 days). In conclusion, the collaborative strategy of CGKRK-PSNPs combined with borneol provided a promising drug delivery routine for glioblastoma therapy.
研究领域:
药学
·
神经肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2019
·
IF 4.137
Chang Sheng,Wang Yanfei,Zhang Tianyi,Pu Xiaohui,Zong Lanlan,Zhu Heyun,Zhao Luling,Feng Bo
The toxicity and side effects of traditional chemotherapeutic drugs are the main causes of chemotherapy failure. To improve the specificity and selectivity of chemotherapeutic drugs for tumor cells, a novel redox-sensitive polymer prodrug, polyethylene glycol-poly (β-benzyl-L-aspartate) (PEG-PBLA)-SS-paclitaxel (PPSP), was designed and synthesized in this study. The PPSP micelle was manufactured via high-speed dispersion stirring and dialysis. The particle size and zeta potential of this prodrug micelle were 63.77 ± 0.91 nm and −25.8 ± 3.24 mV, respectively. The micelles were uniformly distributed and presented a spherical morphology under a transmission electron microscope. In the tumor physiological environment, the particle size of the PPSP micelles and the release rate of paclitaxel (PTX) were significantly increased compared with those of mPEG-PBLA-CC-PTX (PPCP) micelles, reflecting the excellent redox-sensitive activity of the PPSP micelles. The inhibitory effect of PPSP on HepG2, MCF-7 and HL-7702 cell proliferation was investigated with MTT assays, and the results demonstrated that PPSP is superior to PTX with respect to the inhibition of two tumor cell types at different experimental concentration. Simultaneously PPSP has lower toxicity against HL-7702 cells then PTX and PPCP. Moreover, the blank micelle from mPEG-PBLA showed no obvious toxicity to the two tumor cells at different experimental concentrations. In summary, the redox-sensitive PPSP micelle significantly improved the biosafety and the anti-tumor activity of PTX.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 7
·e0180037
·
IF 2.806
Weiping Ji,Bo Wang,Qiuping Fan,Chao Xu,Youwu He,Youfen Chen
Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran- g -indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2016
·
IF 4.843
Qing Chang,Rui Geng,Shanzheng Wang,Ding Qu,Xiangfei Kong
Treatment for multiple myeloma (MM) with a combined strategy of bone and tumor targeting remains a crucial technical challenge due to the incorporation of various functional components into one single system. Here, we developed dioleoyl phosphatidic acid (DOPA)-based paclitaxel (PTX)-loaded liposomes with modifications of alendronate and transferrin (Ald-/Tf-modified PTX-L), which were capable of bone affinity mediated by phosphate groups in DOPA and alendronate, and tumor targeting offered by transferrin. Ald-/Tf-modified PTX-L had clear and well-defined spherical shape with an intermediated size of 118.8 ± 4.8 nm, a highly negative surface charge of −46.9 ± 6.8 mV and a drug entrapment efficiency (DEE) of approximately 80%. When the pH was changed from pH 7.4 to pH 6.5, the accumulative release of PTX from Ald-/Tf-modified PTX-L significantly increased from 26.7 ± 3.7% to 41.7 ± 4.9%. Importantly, liposomes based on DOPA displayed an obviously stronger affinity with hydroxyapatite (HAp) than 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-based liposomes. Compared to PTX-L, Ald-/Tf-modified PTX-L exhibited obvious improvement of cytotoxicity (IC50 = 1.25 ± 0.09 μg/mL), significant enhancement on PTX intracellular accumulation (16.58 ± 0.62 μg/mg) and notable promotion to apoptosis induction (45.21 ± 3.10%) toward myeloma (MM1s) cells. In this study of antitumor efficacy, Ald-/Tf-modified PTX-L with bone-specific targeting showed a significant effect on extending the median survival time (48 days) and terminal survival time (> 58 days) against the MM1S-injected nude mice among all formulations. The results suggested that Ald-/Tf-modified PTX-L had potential as an efficient anticancer drug delivery system for MM therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2016
·Vol. 8
·期 44
·18782-18791
·
IF 7.76
Zhiqiang Lin,Shuxin Xu,Wei Gao,Hongxiang Hu,Meiwan Chen,Yitao Wang,Bing He,Wenbing Dai,Hua Zhang,Xueqing Wang,Anjie Dong,Yuxin Yin,Qiang Zhang
For in situ thermosensitive hydrogels, it is a big challenge to achieve high drug loading, long-term local retention, and effective drug release simultaneously. To address these issues, we combined the strategy of drug nanocrystals (NCs) and thermosensitive hydrogels with higher gel strength. In particular, we developed paclitaxel NC-based hydrogels using PECT, a thermosensitive polymer synthesized by us (PTX-NC-PECT), and a nanoparticle-based system was used as the control (PTX-NP-PECT). First, high levels of PTX could be loaded in both PECT hydrogels. Moreover, in vivo near infrared fluorescence (NIRF) imaging showed that both hydrogel systems were able to maintain the payloads of 1,1-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) at a peri-tumoural site for at least 21 days, much longer than that achieved with the control hydrogel of Pluronic® F127. Furthermore, we observed that PTX-NCs released free PTX more effectively and homogeneously than PTX-NPs in vitro. It was further verified in vivo that the release of DiR from DiR-NC-PECT was more complete than that from DiR-NP-PECT. Finally, PTX-NC-PECT gel demonstrated the strongest anti-tumour efficacy on MCF-7 breast cancer. In conclusion, PTX-NC-PECT hydrogel might be a high-performance thermosensitive hydrogel for local cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Chaoran Xu,Wei He,Yaqi Lv,Chao Qin,Lingjia Shen,Lifang Yin
A prodrug-based nanosystem obtained by formulating prodrug and nanotechnology into a system is one of the most promising strategies to enhance drug delivery for disease treatment. Herein, we report a new nanosystem based on HA–PTX conjugates (HA–PTX Ns), which penetrated across cell membranes into cytosol, thus enhancing paclitaxel (PTX) delivery. HA–PTX Ns were successfully obtained based on HA–PTX, and their average particle size was approximately 200 nm. Importantly, unlike other prodrug-based nanosystems, HA–PTX Ns obtained cellular entry without entrapment within the lysosomal–endosomal system by using pathways including clathrin-mediated endocytosis, microtubule-associated internalization, macropinocytosis and cholesterol-dependence. Due to significant accumulation in tumors, HA–PTX Ns had more than a 4-fold decrease in tumor volume on day 14 in contrast with PTX alone. In conclusion, HA–PTX Ns could enter cells, bypass the lysosomal–endosomal system and improve PTX delivery.
研究领域:
药物递送
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2018
·
IF 4.439
Hui Zhang,Yuqi Li,Deyong Zheng,Shilin Cao,Lihui Chen,Liulian Huang,Huining Xiao
Separating the natural product of paclitaxel from its structural analogs still remains a significant challenge. In this work, a novel molecular imprinting membrane (Cell/SiO 2 -MIM) with specific recognition sites was hierarchically constructed for paclitaxel (PTX) separation. Inspired by mussel, inorganic silica nanoparticles (SiO 2 NPs) were introduced onto the surface of the regenerated cellulose membrane as polymerization platform in an attempt to enhance the permeation flux of the membrane. The specific recognition sites of PTX were constructed on the nanoscale silica surface through the bulk polymerization of vinylpyridine in the presence of PTX as templates, leading to the membrane with the selective recognition ability for the target molecule (PTX). The as-synthesized imprinting membrane exhibited excellent selective adsorption capacity and perm-selectivity towards PTX, with the maximum adsorption amount and separation factor of 46.36 mg/g and 3.77, respectively. Moreover, after six consecutive adsorption and desorption cycles, the membrane maintained the excellent stability and reusability, which facilities its potential application in an industrial scale.
研究领域:
材料科学
·
药物分离工程
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）