目的 制备共载吲哚美辛(IND)和多柔比星(DOX)的还原响应型胶束(HID-NPs),并探究其逆转乳腺癌MCF-7/ADR细胞多药耐药效果。方法 通过酰胺化反应制备基于透明质酸的两亲性物质(HA-SS-PA),用核磁共振氢谱(1H-NMR)对其结构进行确证;采用纳米共沉淀法制备包载IND和DOX的胶束(HID-NPs)。分别采用动态光扫描(DLS)和透射电镜(TEM)对HID-NPs进行了粒径测定和形貌观察;采用透析法测定了HID-NPs响应释药行为;采用激光共聚焦观察了人乳腺癌DOX耐药细胞MCF-7/ADR细胞对HID-NPs的摄取情况;并通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测定了HID-NPs对人乳腺癌MCF-7和MCF-7/ADR细胞的细胞毒性。结果 核磁共振氢谱表明,HA-SS-PA已成功制备;DLS和TEM结果显示,HID-NPs呈圆形,分布均匀,平均粒径为(103±3.2)nm。释药结果表明,HID-NPs具有良好的还原响应性。细胞摄取实验证明,与游离DOX相比,HID-NPs显著增加DOX在MCF-7/ADR细胞内蓄积量;MTT实验表明,HID-NPs能显著杀死MCF-7/ADR细胞。结论 HID-NPs表现出良好的还原响应性和明显的逆转DOX耐药效果,可用于肿瘤多药耐药的治疗。
Abstract
OBJECTIVE To prepare a reduction-responsive nanoparticle (HID-NPs) for indomethacin (IND) and doxorubicin (DOX) delivering and investigate their effects on reversing multidrug resistance in breast cancer. METHODS Hyaluronic acid-based amphiphilic substances (HA-SS-PA) were prepared by amidation reaction, and their structures were confirmed by NMR. HID-NPs were prepared by nano-precipitation method. The particle size measurement and morphology observation of the HID-NPs were measured by dynamic light scanning (DLS) and transmission electron microscopy (TEM), respectively. The reduction-responsive drug release behavior of HID-NPs was determined by dialysis method. Cell uptake HID-NPs on human breast cancer MCF-7/ADR cells were observed by laser confocal microscopy. The cytotoxicity of HID-NPs on human breast cancer MCF-7 and MCF-7/ADR cells was determined by MTT assay. RESULTS 1H-NMR spectrum indicated that HA-SS-PA was successfully prepared. The results of DLS and TEM showed that HID-NPs were round and evenly distributed with an average particle size of (103±3.2) nm. Drug release assay indicates that HID-NPs have good reduction-responsiveness ability. Cell uptake experiments demonstrated that HID-NPs significantly increased DOX accumulation in MCF-7/ADR cells compared with free DOX; MTT assays showed that HID-NPs could significantly destroy MCF-7/ADR cells. CONCLUSION HID-NPs shows good reduction-responsiveness and obvious reverse DOX resistance, which can be used for the treatment of multidrug resistance of breast tumors.
关键词
还原响应型 /
多药耐药 /
吲哚美辛 /
共递送 /
透明质酸
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Key words
reduction-responsive /
multidrug resistance /
indomethacin /
co-delivery /
hyaluronic acid
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中图分类号：
R944
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