An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects
An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects
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DOI：
10.1002/adhm.201500080
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发表时间：
2015-05-13
影响因子：
10
通讯作者：
Mareque-Rivas, Juan C.
中科院分区：
文献类型：
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作者：
Hernandez-Gil, Javier;Cobaleda-Siles, Macarena;Mareque-Rivas, Juan C.
目前主要的兴趣是利用免疫系统对抗癌症，并开发提供补充癌症杀伤机制的药物。尽管最近出现的基于纳米颗粒的药物递送系统已经改善了铂类药物用于化疗的功效，但其设计和使用的基本范例之一是逃避免疫系统的监视以增强抗癌功效。然而，新的研究表明，化疗可以从免疫系统的主动靶向刺激中获益，并且适当功能化的纳米材料可能是克服免疫治疗中一些关键挑战的理想选择。报道了铂（IV）前药修饰的聚乙二醇化磷脂胶束，其封装生物相容性氧化铁纳米颗粒（IONP）作为顺铂的新递送系统。Pt（IV）-IONP用聚肌苷酸-聚胞苷酸（poly（I：C））官能化，所述聚肌苷酸-聚胞苷酸（poly（I：C））是广泛用作癌症免疫疗法的临床试验中的佐剂的双链RNA（dsRNA）类似物。Pt（IV）-IONP和poly（I：C）-Pt（IV）-IONP将前药在不同肿瘤细胞中的细胞毒性提高了一个数量级以上，同时大大提高了顺铂和poly（I：C）激活树突状细胞的能力，树突状细胞是免疫治疗中的关键细胞参与者。结果表明，这些构建体有望用于靶向化学免疫治疗。
There is major current interest in harnessing the immune system against cancer and in developing drugs that provide complementary cancer killing mechanisms. Although the recent advent of nanoparticle-based drug delivery systems has improved the efficacy of platinum drugs for chemotherapy, one of the fundamental paradigms in their design and use is evading surveillance by the immune system to enhance anticancer efficacy. However, new studies are showing that chemotherapy can profit from actively targeting stimulation of the immune system and that suitably functionalized nanomaterials might be ideal for overcoming some key challenges in immunotherapy. Pt(IV) prodrug-modified PEGylated phospholipid micelles that encapsulate biocompatible iron oxide nanoparticles (IONPs) as a new delivery system for cisplatin are reported. The Pt(IV)-IONPs are functionalized with polyinosinic-polycytidylic acid (poly (I:C))a double stranded RNA (dsRNA) analog widely used as an adjuvant in clinical trials of cancer immunotherapy. The Pt(IV)-IONPs and poly (I:C)-Pt(IV)-IONPs enhance by more than an order of magnitude the prodrug cytotoxicity in different tumor cells, while greatly increasing the ability of cisplatin and poly (I:C) to activate dendritic cellsthe key cellular players in immunotherapy. The results suggest that these constructs hold promise for targeted chemoimmunotherapy.