Enhanced anticancer potency by thermo/pH-responsive PCL-based magnetic nanoparticles
Enhanced anticancer potency by thermo/pH-responsive PCL-based magnetic nanoparticles
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DOI：
10.1080/09205063.2017.1414482
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Ramazani, Ali
中科院分区：
文献类型：
--
作者：
Sadr, Samad Hosseini;Davaran, Soodabeh;Ramazani, Ali
为了提供可预测的治疗反应，已经做出了巨大的努力来开发药物载体。此外，联合治疗已成为具有协同效应的临床癌症治疗的有前途的策略。本研究旨在开发一种新的刺激响应性顺磁性纳米载体，用于多柔比星（DOX）和甲氨蝶呤（MTX）的细胞内共递送到MCF 7细胞系。采用开环聚合和自由基聚合相结合的方法，设计并合成了一种新型的温度/pH敏感的两亲性顺磁性纳米复合材料，该材料由疏水的、可生物降解的PCL链段和亲水的、生物相容的P（NIPAAm-co-HEMA-co-MAA-co-TMSPMA）嵌段组成。采用FTIR、HNMR、CNMR、SEM、EDX、TGA和VSM等技术对合成的纳米粒子和中间体的结构和理化性质进行了研究和表征。纳米载体上的DOX和MTX分别达到95.04%和97.29%的包封率。双重药物释放曲线揭示了肿瘤小生境辅助释放行为（在41摄氏度和pH 5.4的温度下观察到更多的药物释放）。通过MTT法、DAPI染色、细胞周期和实时荧光PCR分析证实，DOX/MTX负载纳米复合物的抗肿瘤能力显著高于游离药物。此外，纳米载体对MCF 7细胞系的细胞毒性测定揭示了其作为抗癌药物纳米载体的适合性。结果表明，与游离药物相比，这种工程化的双重抗癌药物递送系统确保了增加的抗肿瘤活性以及降低的毒性。
Great efforts have been made to develop drug carriers with the aim of providing predictable therapeutic response. Moreover, combination therapies have become promising strategies for clinical cancer treatment with synergistic effects. The present study purposed to develop a new stimuli-responsive paramagnetic nanocarrier for the intracellular co-delivery of doxorubicin (DOX) and methotrexate (MTX) to the MCF7 cell line. A novel thermo/pH-sensitive amphiphilic paramagnetic nanocomposite comprised of hydrophobic and biodegradable PCL segments and a hydrophilic biocompatible P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) block was designed and synthesized by combining the ring opening and free radical polymerization methods. The structure and physic-chemical characterization of synthesized nanoparticles and intermediates were studied and revealed using FTIR, HNMR, CNMR, SEM, EDX, TGA, and VSM techniques. DOX and MTX on a nanocarrier achieved 95.04 and 97.29% encapsulation efficiency, respectively. The dual drug release profile revealed tumor niche-assisted release behavior (more drug release was observed at a temperature of 41 degrees C and pH5.4). The antitumor ability of the DOX/MTX-loaded nanocomposite was significantly higher than that of free drugs, confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR analysis on MCF7 cell lines. Furthermore, the cytotoxicity assay of a nanocarrier to the MCF7 cell line revealed its suitability as an anticancer drug nanocarrier. The results indicated that this engineered dual anticancer drug delivery system ensures increased antitumor activity as well as decreased toxicity in comparison with the free drugs.