pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time
pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time
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DOI：
10.1016/j.biomaterials.2018.04.002
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发表时间：
2018-07-01
期刊：
影响因子：
14
通讯作者：
Wu, Aiguo
中科院分区：
文献类型：
--
作者：
Jiang, Zhenqi;Tian, Yuchen;Wu, Aiguo
基于纳米颗粒的肿瘤治疗被广泛研究；然而，由于药物过早泄漏、脱靶效应和组织穿透性差，很少有能够提高患者生存时间的药物。此前，我们成功合成了一个新的Y-1受体（Y1R）配体修饰的光致发光BPLP纳米泡和纳米颗粒家族，用于靶向乳腺癌超声成像；然而，在肝脏、肾脏和脾脏中也可以观察到堆积增加，这表明颗粒在体内与巨噬细胞有显著的相互作用。在此，我们首次通过引入基于CD47人糖蛋白的自肽，赋予Y1R配体功能化的BPLP-WPU聚合物胶束抗吞噬能力。在体内应用自肽修饰的、负载DOX的胶束，在100天的治疗中获得了100%的存活率和完全的肿瘤坏死。装载SPION的自肽修饰胶束的体内成像显示有效靶向肿瘤部位，而铁含量分析显示肝脏和肾脏中的颗粒积聚减少，巨噬细胞相互作用减少，肿瘤中的颗粒增加2倍。这些结果表明，Y1R配体、自肽修饰的BPLP-WPU胶束能够靶向特异性肿瘤治疗和成像，使其成为临床提高生存率和肿瘤减量的理想候选者。(C) 2018 Elsevier Ltd.版权所有。
Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y-1 receptor (Y1R) ligand modified, photo luminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo. Herein, for the first time, we imparted antiphagocytosis capability to Y1R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y1R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically. (C) 2018 Elsevier Ltd. All rights reserved.