Enhanced therapeutic efficacy of iRGD-conjugated crosslinked multilayer liposomes for drug delivery.
Enhanced therapeutic efficacy of iRGD-conjugated crosslinked multilayer liposomes for drug delivery.
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DOI：
10.1155/2013/378380
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发表时间：
2013
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Liu Y;Ji M;Wong MK;Joo KI;Wang P
通过结合各种特异性配体的靶向纳米颗粒在纳米医学中显示出潜在的治疗功效。然而，抗肿瘤药物对实体瘤的渗透性差仍然是一个主要障碍。在这里，我们描述了一种靶向策略，通过共轭交联多层脂质体囊泡（cMLV）制剂与肿瘤穿透肽，iRGD的抗肿瘤药物输送。结果表明，iRGD肽可以促进载药cMLV的结合和细胞摄取，从而增强乳腺肿瘤细胞（包括多药耐药细胞）的抗肿瘤功效。此外，共定位数据显示，iRGD-cMLV通过网格蛋白介导的途径进入细胞，然后通过内体-溶酶体转运进行有效的药物递送。最后，体内研究表明iRGD-cMLV可以有效地递送抗癌药物以介导显著的肿瘤抑制。
Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.