α(V)β(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug.
α(V)β(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug.
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DOI：
10.1021/nn301148e
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发表时间：
2012-05-22
期刊：
影响因子：
17.1
通讯作者：
Lippard SJ
中科院分区：
文献类型：
--
作者：
Graf N;Bielenberg DR;Kolishetti N;Muus C;Banyard J;Farokhzad OC;Lippard SJ
将治疗药物靶向递送至肿瘤新生血管可能是一种选择性癌症治疗的有效方法。整合素是参与细胞黏附和细胞信号传导的异二聚体跨膜蛋白，其在癌症和炎症性疾病中通常表达上调。αvβ3整合素在血管生成内皮细胞以及许多癌细胞上差异上调。在此，我们展示了使用环五肽c(RGDfK)将顺铂前药包封的聚（D,L - 乳酸 - 羟基乙酸） - 嵌段 - 聚乙二醇（PLGA - PEG）纳米粒子（NPs）对癌细胞上的αvβ3整合素进行差异靶向。顺铂是使用最广泛的抗癌药物之一，能够提高其治疗指数的方法具有广泛的重要性。与常规剂型的顺铂相比，RGD靶向的包封Pt(IV)的纳米粒子在体外前列腺和乳腺癌上皮细胞模型中显示出更强的细胞毒性。与先前报道的系统（一种小分子Pt(IV) - RGD偶联物和一种带有RGD部分的Pt(IV)纳米级配位聚合物）相比，其细胞毒性也有所提高。这一结果也促使我们在动物模型中评估这种新构建体的抗癌效果。在体内原位人乳腺癌异种移植模型中，与顺铂相比，RGD靶向的PLGA - PEG纳米粒子更有效且耐受性更好。
Targeted delivery of therapeutics to tumor neovasculature is potentially a powerful approach for selective cancer treatment. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and cell signaling, and their expression is commonly upregulated in cancers and inflammatory diseases. The αvβ3 integrin is differentially upregulated on angiogenic endothelial cells as well as on many cancer cells. Here we demonstrate the differential targeting of cisplatin prodrug-encapsulated poly(D,L-lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) to the αvβ3 integrin on cancer cells using the cyclic pentapeptide c(RGDfK). Cisplatin is one of the most widely used anticancer drugs and approaches that can improve its therapeutic index are of broad importance. The RGD-targeted Pt(IV)-encapsulated NPs displayed enhanced cytotoxicity as compared to cisplatin administered in its conventional dosage form in model prostate and breast cancer epithelial cells in vitro. Cytotoxicities were also elevated in comparison to those of previously reported systems, a small molecule Pt(IV)-RGD conjugate and a Pt(IV) nanoscale coordination polymer carrying RGD moieties. This result encouraged us also to evaluate the anticancer effect of the new construct in an animal model. The RGD-targeted PLGA-PEG NPs were more efficacious and better tolerated by comparison to cisplatin in an orthotopic human breast cancer xenograft model in vivo.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
11
作者：
Basma, H;El-Refaey, H;Cheng, PW
通讯作者：
Cheng, PW
影响因子：
10.8
作者：
Fonseca, C;Simoes, S;Gaspar, R
通讯作者：
Gaspar, R
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R
DOI：
10.1073/pnas.1011379108
发表时间：
2011-02-01
影响因子：
11.1
作者：
Dhar, Shanta;Kolishetti, Nagesh;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.