Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer.
Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer.
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DOI：
10.1016/j.biomaterials.2014.09.017
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发表时间：
2015-01
期刊：
影响因子：
14
通讯作者：
Lin, Wenbin
中科院分区：
文献类型：
--
作者：
He, Chunbai;Liu, Demin;Lin, Wenbin
对化疗剂顺铂的抗性是成功治疗许多癌症的主要限制。开发新的策略来克服对化疗的内在和获得性抗性对于卵巢癌和其他类型的癌症的有效治疗至关重要。我们已经寻求通过使用自组装的纳米级配位聚合物（NCP）共递送化疗剂和靶向多药耐药（MDR）基因的汇集的siRNA来使耐药卵巢癌细胞对化疗重新敏感。在这项工作中，NCP-1触发释放性能的颗粒首先构建通过连接顺铂前药为基础的双膦酸盐桥接配体与锌2+金属连接点，然后用阳离子脂质层，随后通过吸附池siRNA靶向三个MDR基因，包括生存素，Bcl-2，和P-糖蛋白通过静电相互作用。所得到的NCP-1/siRNA颗粒促进顺铂和siRNA的细胞摄取，并在顺铂耐药卵巢癌细胞中实现有效的内体逃逸。细胞活力测定、DNA梯状条带和流式细胞术显示，NCP-1/siRNA通过下调MDR基因的表达增强了化疗效果。局部施用NCP-1/siRNA有效地减小了顺铂耐药SKOV-3皮下异种移植物的肿瘤大小。这项工作表明，NCP-1/siRNA平台在增强化疗疗效以有效治疗耐药癌症方面具有很大的前景。
Resistance to the chemotherapeutic agent cisplatin is a major limitation for the successful treatment of many cancers. Development of novel strategies to overcome intrinsic and acquired resistance to chemotherapy is of critical importance to effective treatment of ovarian cancer and other types of cancers. We have sought to re-sensitize resistant ovarian cancer cells to chemotherapy by co-delivering chemotherapeutics and pooled siRNAs targeting multi-drug resistance (MDR) genes using self-assembled nanoscale coordination polymers (NCPs). In this work, NCP-1 particles with trigger release properties were first constructed by linking cisplatin prodrug-based bisphosphonate bridging ligands with Zn2+ metal-connecting points and then coated with a cationic lipid layer, followed by the adsorption of pooled siRNAs targeting three MDR genes including survivin, Bcl-2, and P-glycoprotein via electrostatic interactions. The resulting NCP-1/siRNA particles promoted cellular uptake of cisplatin and siRNA and enabled efficient endosomal escape in cisplatin-resistant ovarian cancer cells. By down-regulating the expression of MDR genes, NCP-1/siRNAs enhanced the chemotherapeutic efficacy as indicated by cell viability assay, DNA ladder, and flow cytometry. Local administration of NCP-1/siRNAs effectively reduced tumor sizes of cisplatin-resistant SKOV-3 subcutaneous xenografts. This work shows that the NCP-1/siRNA platform holds great promise in enhancing chemotherapeutic efficacy for the effective treatment of drug-resistant cancers.
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影响因子：
17.1
作者：
Bhirde, Ashwin A.;Patel, Vyomesh;Gavard, Julie;Zhang, Guofeng;Sousa, Alioscka A.;Masedunskas, Andrius;Leapman, Richard D.;Weigert, Roberto;Gutkind, J. Silvio;Rusling, James F.
通讯作者：
Rusling, James F.
DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.5
作者：
Herzog, TJ
通讯作者：
Herzog, TJ
影响因子：
13.3
作者：
Cho, Young-Seok;Lee, Gee Young;Sajja, Hari Krishna;Qian, Weiping;Cao, Zehong;He, Weiling;Karna, Prasanthi;Chen, Xiaoyuan;Mao, Hui;Wang, Y. Andrew;Yang, Lily
通讯作者：
Yang, Lily
DOI：
10.1039/c2cc17635a
发表时间：
2012-03-11
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Liu D;Kramer SA;Huxford-Phillips RC;Wang S;Della Rocca J;Lin W
通讯作者：
Lin W