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Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.
Advanced Science ( IF 14.3 ) Pub Date : 2020-01-20 , DOI: 10.1002/advs.201903290 Gan Jiang 1 , Huan Chen 1, 2 , Jialin Huang 1, 3 , Qingxiang Song 1 , Yaoxing Chen 1 , Xiao Gu 1 , Zhenhuan Jiang 1 , Yukun Huang 4 , Yingying Lin 3 , Junfeng Feng 3 , Jiyao Jiang 3 , Yinghui Bao 3 , Gang Zheng 5 , Jun Chen 4 , Hongzhuan Chen 1, 2 , Xiaoling Gao 1
Advanced Science ( IF 14.3 ) Pub Date : 2020-01-20 , DOI: 10.1002/advs.201903290 Gan Jiang 1 , Huan Chen 1, 2 , Jialin Huang 1, 3 , Qingxiang Song 1 , Yaoxing Chen 1 , Xiao Gu 1 , Zhenhuan Jiang 1 , Yukun Huang 4 , Yingying Lin 3 , Junfeng Feng 3 , Jiyao Jiang 3 , Yinghui Bao 3 , Gang Zheng 5 , Jun Chen 4 , Hongzhuan Chen 1, 2 , Xiaoling Gao 1
Affiliation
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Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein-like nanostructure is developed to amplify their internalization into GICs through receptor-stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor-stimulated macropinocytosis pathway in GICs, this CXCR4 receptor-stimulated lipoprotein-like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA-34a in the core, this tailored SLNP reduces sex-determining region Y-box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs-bearing mice. Taken together, a tailored lipoprotein-based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor-stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.
中文翻译：
定制的脂蛋白样 miRNA 递送纳米结构通过受体刺激的巨胞饮作用抑制神经胶质瘤干性和耐药性。
神经胶质瘤起始细胞（GIC）充当神经胶质瘤繁殖和复发的种子。设计一种智能且有效的策略来靶向 GIC 并抑制与干性和化疗耐药性相关的多种信号通路对于实现癌症治愈至关重要。受 GIC、分化的神经胶质瘤细胞和正常细胞之间内吞作用代谢差异的启发，开发了一种定制的脂蛋白样纳米结构，通过受体刺激的巨胞饮作用放大它们对 GIC 的内化。由于CXCR4在GIC和胶质瘤肿瘤部位高表达，同时CXCR4的激活诱导GIC中受体刺激的巨胞饮途径，因此CXCR4受体刺激的脂蛋白样纳米颗粒（SLNP）在体外和体内实现了GIC中的高效积累。通过在核心中携带 microRNA-34a，这种定制的 SLNP 减少了性别决定区 Y-box 2 和 Notch1 的表达，有力地抑制了 GIC 的干性和化疗耐药性，并显着延长了 GIC 携带小鼠的生存期。总而言之，基于脂蛋白的定制纳米结构通过受体刺激的巨胞饮作用实现了有效的 GIC 积累和治疗效果，为 RNA 干扰药物对抗神经胶质瘤提供了强大的纳米平台。
更新日期：2020-01-21
中文翻译：
定制的脂蛋白样 miRNA 递送纳米结构通过受体刺激的巨胞饮作用抑制神经胶质瘤干性和耐药性。
神经胶质瘤起始细胞（GIC）充当神经胶质瘤繁殖和复发的种子。设计一种智能且有效的策略来靶向 GIC 并抑制与干性和化疗耐药性相关的多种信号通路对于实现癌症治愈至关重要。受 GIC、分化的神经胶质瘤细胞和正常细胞之间内吞作用代谢差异的启发，开发了一种定制的脂蛋白样纳米结构，通过受体刺激的巨胞饮作用放大它们对 GIC 的内化。由于CXCR4在GIC和胶质瘤肿瘤部位高表达，同时CXCR4的激活诱导GIC中受体刺激的巨胞饮途径，因此CXCR4受体刺激的脂蛋白样纳米颗粒（SLNP）在体外和体内实现了GIC中的高效积累。通过在核心中携带 microRNA-34a，这种定制的 SLNP 减少了性别决定区 Y-box 2 和 Notch1 的表达，有力地抑制了 GIC 的干性和化疗耐药性，并显着延长了 GIC 携带小鼠的生存期。总而言之，基于脂蛋白的定制纳米结构通过受体刺激的巨胞饮作用实现了有效的 GIC 积累和治疗效果，为 RNA 干扰药物对抗神经胶质瘤提供了强大的纳米平台。
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