A redox-sensitive micelle-like nanoparticle self-assembled from amphiphilic adriamycin-human serum albumin conjugates for tumor targeted therapy.

A redox-sensitive micelle-like nanoparticle self-assembled from amphiphilic adriamycin-human serum albumin conjugates for tumor targeted therapy.
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由两亲性阿霉素-人血清白蛋白缀合物自组装的氧化还原敏感胶束状纳米粒子,用于肿瘤靶向治疗

DOI:
10.1155/2015/987404
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发表时间:
2015
影响因子:
--
通讯作者:
Li W
Li W
中科院分区:
生物学3区
文献类型:
--
作者:
Chen L;Chen F;Zhao M;Zhu X;Ke C;Yu J;Yan Z;Zhang F;Sun Y;Chen D;Jiang C;Zhao X;Gao Y;Guo S;Li W

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化疗药物阿霉素(ADR)的高毒性和难溶性限制了其在肿瘤治疗中的应用。纳米医学为克服这些缺点提供了新的希望。但如何提高体内稳定性和控制细胞内药物释放是纳米制剂的关键问题。本文通过二硫键3-(2-吡啶二硫基)丙酰肼(PDPH)将疏水性ADR与生物相容性人血清白蛋白(HSA)成功连接,得到两亲性HSA-ADR。由此组装的新型ADR-HSA胶束NPs表现出具有谷胱甘肽(GSH)敏感性接头的明确定义的稳定核壳结构。细胞外水平的稳定PDPH连接体被细胞内水平的GSH破坏,具有受控的ADR释放曲线。氧化还原敏感的ADR-HSA纳米粒对胃癌细胞(NCI-N87)的体外细胞毒性明显增强。此外,如通过IVIS Lumina II成像系统(Xenogen)所观察到的,由于其高稳定性,ADR-HSA NP的肿瘤内积累比HSA/ADR NP高得多。因此,在对携带胃肿瘤的Balb/c裸小鼠静脉给药后,体内肿瘤抑制显著增强。这些体外/体内结果表明,含二硫键的ADR-HSA纳米粒是一种有效的癌症治疗纳米药物递送系统。
The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.
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