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首页> 外文期刊>Biomaterials Science >CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer
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CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer

机译：CD44针对氧化还原触发的自组装，具有磁性增强的EPR效应，用于有效扩增甘甜酸，治疗三阴性乳腺癌

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摘要

Gambogic acid (GA) is a natural anti-tumor drug whose application is restricted by its poor aqueous solubility and inefficient bioavailability. Developing nanomaterials with excellent biocompatibility can amplify the therapeutic effects of GA. In this study, a tumor-targeted redox controllable self-assembled nano-system with magnetic enhanced EPR effects (mPEG-HA/CSO-SS-Hex/SPION/GA) was developed to improve the anticancer efficacy of GA. The nano-system is constituted by three layers: the outer layer is mono-aminated poly(ethylene glycol) grafted hyaluronic acid (mPEG-HA), which can target the CD44 receptor in breast cancer cells; the middle layer consists of disulfide linked hexadecanol (Hex) and chitosan oligosaccharide (CSO) to control the drug release by reduction response; the core layer is superparamagnetic iron oxide nanoparticles (SPION), which can enhance the EPR effect by magnetic guidance and contribute to GA entrapment. Different experiments were performed to characterize the complex self-assembly, and the cytotoxicity, pharmacokinetics, and in vivo antitumor activity of the self-assembly were investigated to evaluate its anti-tumor effects. The results revealed that mPEG-HA/CSO-SS-Hex/SPION/GA is an excellent nanosystem with appropriate size and sensitive responsiveness; it can accumulate in tumor sites and achieve excellent therapeutic effects on triple-negative breast cancer (TNBC). In summary, a CD44-targeted redox-triggered self-assembly nanosystem with magnetic enhanced EPR effects was developed for effective amplification of GA; it has potential to act as an effective carrier in drug delivery for chemotherapy of TNBC.
机译：甘伐酸（Ga）是一种天然的抗肿瘤药物，其应用受其差的水溶性和低效率的生物利用度限制。具有优异生物相容性的纳米材料可以扩增Ga的治疗效果。在该研究中，开发了一种具有磁性增强EPR效应的肿瘤靶向氧化还原可控自组装纳米系统（MPEG-HA / CSO-SS-SS-SPION / GA），以改善GA的抗癌效果。纳米系统由三层构成：外层是单胺化聚（乙二醇）接枝透明质酸（MPEG-HA），其可以靶向乳腺癌细胞中的CD44受体;中间层由二硫化物连接的十六烷醇（六十六烷基醇（六十六烷）和壳聚糖寡糖（CSO）组成，以通过还原反应控制药物释放;芯层是超顺磁性氧化铁纳米颗粒（Spion），其可以通过磁引导增强EPR效应并有助于GA陷阱。进行不同的实验以表征复杂的自组装，并研究了细胞毒性，药代动力学和体内抗肿瘤活性的自组装，以评估其抗肿瘤作用。结果表明，MPEG-HA / CSO-SS-HEX / SPION / GA是具有适当尺寸和敏感响应性的优异纳米系统;它可以积聚在肿瘤部位，并对三阴性乳腺癌（TNBC）达到优异的治疗效果。总之，开发了一种具有磁性增强EPR效应的CD44靶向氧化还原的自组装纳米系统，用于有效扩增Ga;它有可能作为TNBC化疗的药物递送的有效载体。

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  • 来源
    《Biomaterials Science》 |2020年第1期|共12页
  • 作者

    Sang Mangmang; Han Lingfei; Luo Renjie; Qu Wei; Zheng Feng; Zhang Kaigang; Liu Fulei; Xue Jingwei; Liu Wenyuan; Feng Feng;

  • 作者单位

    China Pharmaceut Univ Minist Educ Key Lab Drug Qual Control &

    Pharmacovigilance Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Minist Educ Key Lab Drug Qual Control &

    Pharmacovigilance Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Minist Educ Key Lab Drug Qual Control &

    Pharmacovigilance Nanjing 210009 Peoples R China;

    Chinese Pharmaceut Univ Joint Lab Tai An 271000 Shandong Peoples R China;

    China Pharmaceut Univ Minist Educ Key Lab Drug Qual Control &

    Pharmacovigilance Nanjing 210009 Peoples R China;

    Chinese Pharmaceut Univ Joint Lab Tai An 271000 Shandong Peoples R China;

    Chinese Pharmaceut Univ Joint Lab Tai An 271000 Shandong Peoples R China;

    Chinese Pharmaceut Univ Joint Lab Tai An 271000 Shandong Peoples R China;

    China Pharmaceut Univ Minist Educ Key Lab Drug Qual Control &

    Pharmacovigilance Nanjing 210009 Peoples R China;

    Chinese Pharmaceut Univ Joint Lab Tai An 271000 Shandong Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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