Investigation on a smart nanocarrier with a mesoporous magnetic core and thermoresponsive shell for co-delivery of doxorubicin and curcumin: a new approach towards combination therapy of cancer
Investigation on a smart nanocarrier with a mesoporous magnetic core and thermoresponsive shell for co-delivery of doxorubicin and curcumin: a new approach towards combination therapy of cancer
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DOI：
10.1039/c7ra03735j
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发表时间：
2017-01-01
期刊：
影响因子：
3.9
通讯作者：
Das, Dibakar
中科院分区：
文献类型：
--
作者：
Asghar, Khushnuma;Qasim, Mohd;Das, Dibakar
在这项工作中，我们报道了一种新型智能纳米载体的合成和表征，该纳米载体具有介孔磁核和热响应壳，用于共同递送亲水性阿霉素（Dox）和疏水性姜黄素（Cur），作为癌症治疗的联合疗法。在氧化剂和交联剂的作用下，在预先合成的介孔Fe3O4纳米颗粒（MIO NPs）表面，将NIPAM和MAm原位交联聚合制备了P（NIPAM-MAm）包覆的介孔Fe3O4纳米复合材料（MIO-P(NIPAM-MAm)）。以CTAB为牺牲软模板，采用共沉淀法合成了MIO NPs。采用不同的表征技术研究了MIO纳米粒子和MIO- p （NIPAMMAm）纳米复合材料的物理化学性质。TEM测定的纳米复合材料的粒径在200 ~ 500 nm之间。VSM结果表明，MIO和MIO- p （NIPAM-MAm）纳米复合材料具有超顺磁性。MIO-P（NIPAM-MAm）纳米复合材料的临界溶液温度（LCST）较低，为41摄氏度，与纯PNIPAM纳米载体不同，它适用于受控药物递送应用。Dox和Cur的包封率分别为96%和90%。MIO-P(nipam - mom)-Cur-Dox的温度依赖性释放研究表明，药物（Dox和Cur）在LCST以下释放较慢，在LCST以上持续释放。采用不同的数学模型（如零阶、一阶、Higuchi和Korsmeyer-Peppas）拟合两种药物的实验释放曲线。对正常细胞和HeLa细胞的MTT试验表明，MIO-P（NIPAM-MAm）纳米复合材料无毒。与游离Dox、游离Cur和游离Dox +游离Cur混合物相比，共负载的MIOP(nipam - mom)-Cur-Dox纳米复合材料具有更高的体外抗癌活性。这种共载智能给药系统在癌症诊断中具有控制和靶向给药的潜力。
In this work, we report on the synthesis and characterization of a novel and smart nanocarrier with a mesoporous magnetic core and thermo-responsive shell for co-delivery of hydrophilic doxorubicin (Dox) and hydrophobic curcumin (Cur) as a combinational therapy for cancer treatment. The P(NIPAMMAm) coated mesoporous Fe3O4 (MIO-P(NIPAM-MAm)) nanocomposite was prepared by in situ cross linked polymerization of NIPAM and MAm on the surface of pre-synthesized mesoporous Fe3O4 nanoparticles (MIO NPs) in the presence of an oxidizer and cross linker. MIO NPs were synthesised by co-precipitation method using CTAB as the sacrificial soft template. Different characterization techniques have been used to study the physicochemical properties of MIO NPs and the MIO-P(NIPAMMAm) nanocomposite. Particle sizes of the MIO-P(NIPAM-MAm) nanocomposite estimated by TEM were found to be in between 200-500 nm. VSM results show MIO and MIO-P(NIPAM-MAm) nanocomposites to be superparamagnetic in nature. MIO-P(NIPAM-MAm) nanocomposites exhibited a lower critical solution temperature (LCST) of 41 degrees C, which is suitable for controlled drug delivery applications unlike pure PNIPAM based nanocarriers. The encapsulation efficiency of Dox and Cur were found to be 96% and 90% respectively. Temperature dependent release studies from MIO-P(NIPAM-MAm)-Cur-Dox indicated a slower release of drugs (both Dox and Cur) below LCST and a sustained release above LCST. Different mathematical models (such as zero order, first order, Higuchi and Korsmeyer-Peppas) were used to fit the experimental release profiles of both drugs. MTT assays on normal and HeLa cells demonstrated the non-toxic nature of the MIO-P(NIPAM-MAm) nanocomposite. The co-loaded MIOP( NIPAM-MAm)-Cur-Dox nanocomposite exhibited higher in vitro anti-cancer activity compared to free Dox, free Cur, and a free Dox + free Cur mixture. Such a co-loaded smart delivery system could have potential for controlled and targeted drug delivery in cancer diagnosis.