Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells
Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells
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DOI：
10.1016/j.ijpharm.2013.09.032
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发表时间：
2013-12-15
影响因子：
5.8
通讯作者：
Taratula, Oleh
中科院分区：
文献类型：
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作者：
Taratula, Olena;Dani, Raj Kumar;Taratula, Oleh
本研究开发了一种多功能肿瘤靶向给药系统，并评价了其对化疗和温热治疗相结合的耐药卵巢癌的有效治疗效果。基于工程氧化铁纳米颗粒（IONP）的纳米载体作为多柔比星的有效递送载体，并在暴露于交变磁场（AMF）时提供远程加热癌细胞的能力。纳米载体另外用聚乙二醇和LHRH肽修饰以改善其生物相容性和靶向肿瘤细胞的能力。合成的递送系统具有97.1 nm的平均尺寸和接近于零的ζ电位，这两个参数有利于增加生物介质中的稳定性和减少免疫系统的消除。纳米载体在模拟肿瘤环境的酸性条件下表现出更快的药物释放。同时观察到LHRH靶向给药系统能有效进入卵巢癌耐药细胞，并在荧光显微镜下追踪阿霉素的去向。在暴露于AMF下由IONP产生的轻度高温（40 ℃）协同地增加了由所开发的纳米载体递送到癌细胞的阿霉素的细胞毒性。因此，开发的基于IONP的递送系统在通过组合方法有效治疗卵巢癌方面具有很高的潜力。(C)2013爱思唯尔有限公司版权所有。
A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40 C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. (C) 2013 Elsevier B.V. All rights reserved.