Tumor Targeting Synergistic Drug Delivery by Self-Assembled Hybrid Nanovesicles to Overcome Drug Resistance
Tumor Targeting Synergistic Drug Delivery by Self-Assembled Hybrid Nanovesicles to Overcome Drug Resistance
复制标题
通过自组装混合纳米囊泡靶向肿瘤协同药物递送以克服耐药性
DOI：
10.1007/s11095-016-2051-9
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发表时间：
2017-01-01
影响因子：
3.7
通讯作者：
Cheng, Si-Xue
中科院分区：
文献类型：
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作者：
Gong, Meng-Qing;Wu, Cong;Cheng, Si-Xue
为了克服肿瘤化疗中的多药耐药（MDR）问题，开发了一种具有肿瘤靶向性和提高细胞摄取效率的聚合物/无机混合给药平台。为了评估我们的递送平台对不同耐药抑制剂递送的适用性，我们将两种双药对（多柔比星/丁硫氨酸亚砜胺和多柔比星/tariquidar）分别装载在肝素-生物素/肝素/硫酸鱼精蛋白/碳酸钙纳米囊泡中，实现抗癌药物和耐药抑制剂同时递送至耐药肿瘤细胞。通过自组装制备的载药杂化纳米囊泡平均粒径小于210 nm， zeta电位为负，在含血清的水介质中表现出良好的稳定性。体外细胞毒性评价表明，具有肿瘤靶向生物素片段的杂化纳米囊泡具有增强的肿瘤细胞抑制作用。此外，与多柔比星（DOX）单药负载的纳米囊泡相比，双药负载的混合纳米囊泡表现出明显更强的细胞生长抑制作用，这是由于丁硫氨酸亚砜胺（BSO）降低了细胞内谷胱甘肽（GSH）含量，或tariquarar （TQR）抑制了p -糖蛋白（P-gp）。本研究制备的肿瘤靶向纳米囊泡可同时递送多种药物并有效逆转耐药，在肿瘤药物递送中具有广阔的应用前景。本研究开发的聚合物/无机杂化给药平台，对于不同抗肿瘤药物/耐药抑制剂对的共给药，克服MDR具有良好的适用性。
To overcome multi-drug resistance (MDR) in tumor chemotherapy, a polymer/inorganic hybrid drug delivery platform with tumor targeting property and enhanced cell uptake efficiency was developed.To evaluate the applicability of our delivery platform for the delivery of different drug resistance inhibitors, two kinds of dual-drug pairs (doxorubicin/buthionine sulfoximine and doxorubicin/tariquidar, respectively) were loaded in heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles to realize simultaneous delivery of an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells.Prepared by self-assembly, the drug loaded hybrid nanovesicles with a mean size less than 210 nm and a negative zeta potential exhibit good stability in serum contained aqueous media. The in vitro cytotoxicity evaluation indicates that hybrid nanovesicles with tumor targeting biotin moieties have an enhanced tumor cell inhibitory effect. In addition, dual-drug loaded hybrid nanovesicles exhibit significantly stronger cell growth inhibition as compared with doxorubicin (DOX) mono-drug loaded nanovesicles due to the reduced intracellular glutathione (GSH) content by buthionine sulfoximine (BSO) or the P-glycoprotein (P-gp) inhibition by tariquidar (TQR).The tumor targeting nanovesicles prepared in this study, which can simultaneously deliver multiple drugs and effectively reverse drug resistance, have promising applications in drug delivery for tumor treatments. The polymer/inorganic hybrid drug delivery platform developed in this study has good applicability for the co-delivery of different anti-tumor drug/drug resistance inhibitor pairs to overcome MDR.