A multifunctional poly(curcumin) nanomedicine for dual-modal targeted delivery, intracellular responsive release, dual-drug treatment and imaging of multidrug resistant cancer cells.
A multifunctional poly(curcumin) nanomedicine for dual-modal targeted delivery, intracellular responsive release, dual-drug treatment and imaging of multidrug resistant cancer cells.
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一种多功能聚姜黄素纳米药物，用于双模式靶向递送、细胞内响应释放、双药治疗和多药耐药癌细胞成像。
DOI：
10.1039/c5tb02450a
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发表时间：
2016-05-07
期刊：
影响因子：
--
通讯作者：
Guo S
中科院分区：
文献类型：
--
作者：
Wang J;Wang F;Li F;Zhang W;Shen Y;Zhou D;Guo S
为了克服乳腺癌MCF-7/ADR细胞对紫杉醇的耐药性，开发了一种多功能抗癌纳米药物PTX/MNPs/Qds@Biotin-PEG-PCDA，并进行了同步成像。基于生物素-聚乙二醇聚(姜黄素-二硫代二丙酸)(生物素-聚乙二醇-二硫代二丙酸)聚合物纳米载体(生物素-聚乙二醇-二硫代二丙酸)，负载紫杉醇(PTX)、磁性纳米颗粒(MNPs)和量子点(Qds)的多功能抗癌纳米药物。它结合了有效的靶向传递和摄取(通过生物素和MNP)、细胞内响应释放(通过可切割的PCDA聚合物)、荧光成像(通过QD)和PTX-姜黄素双药联合治疗的优点，从而克服了模型多药耐药乳腺癌细胞(MCF-7/ADR)的耐药机制。PTX/MNPs/Qds@Biotin-PEG-PCDA纳米粒子在生理条件下高度稳定，但在10 mM谷胱甘肽(GSH)存在下可迅速分解释放其载药量。这些纳米颗粒显示出肿瘤细胞从磁靶向和生物素受体介导的内化的组合效应中的高摄取率。此外，PCDA的胞内裂解产物姜黄素可有效下调P-糖蛋白(P-gp)等药物外排转运体的表达，增加PTX在靶细胞内的蓄积，从而增强PTX诱导的细胞毒作用和对MCF-7/ADR细胞的治疗效果。综上所述，这种新型的肿瘤靶向和可追踪的多功能纳米药物在细胞水平上对模型MDR癌症非常有效。
A multifunctional anti-cancer nanomedicine PTX/MNPs/QDs@Biotin–PEG–PCDA was developed aiming at overcoming paclitaxel resistance in MCF-7/ADR breast cancer cells with simultaneous imaging. A multifunctional anti-cancer nanomedicine based on a biotin–poly(ethylene glycol)–poly(curcumin-dithio dipropionic acid) (Biotin–PEG–PCDA) polymeric nanocarrier loaded with paclitaxel (PTX), magnetic nanoparticles (MNPs) and quantum dots (QDs) is developed. It combines advantageous properties of efficient targeted delivery and uptake (via biotin and MNP), intracellular responsive release (via cleavable PCDA polymer), fluorescence imaging (via QD) and combined PTX-curcumin dual-drug treatment, allowing for overcoming drug resistance mechanisms of model multidrug resistant breast cancer cells (MCF-7/ADR). The PTX/MNPs/QDs@Biotin–PEG–PCDA nanoparticles are highly stable under physiological conditions, but are quickly disassembled to release their drug load in the presence of 10 mM glutathione (GSH). The nanoparticles show high uptake by tumour cells from a combined effect of magnet targeting and biotin receptor-mediated internalization. Moreover, curcumin, an intracellularly cleaved product of PCDA, can effectively down regulate the expression of drug efflux transporters such as P-glycoprotein (P-gp) to increase PTX accumulation within target cancer cells, thereby enhancing PTX induced cytotoxicity and therapeutic efficacy against MCF-7/ADR cells. Taken together, this novel tumour-targeting and traceable multifunctional nanomedicine is highly effective against model MDR cancer at the cellular level.