RES blockade: A strategy for boosting efficiency of nanoparticle drug
RES blockade: A strategy for boosting efficiency of nanoparticle drug
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DOI：
10.1016/j.nantod.2014.12.003
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发表时间：
2015-02-01
期刊：
影响因子：
17.4
通讯作者：
Chen, I-Wei
中科院分区：
文献类型：
--
作者：
Liu, Ting;Choi, Hoon;Chen, I-Wei
三十年来，人们一直在大力研究纳米颗粒用于药物输送，但尽管纳米颗粒制造领域在材料、粒径、表面物理化学和靶向部分等方面进行了大量创新，但其输送效率仍然很低。造成这种不足的一个主要原因是它们被肝脏、脾脏、肺、淋巴结等的网状内皮系统（RES）无意中摄取，这与预期目标相竞争。在这里，我们展示了商业脂质体对 RES 的暂时阻断，可显着延迟血液清除并增加小尺寸聚乙二醇化纳米颗粒的肿瘤积累。 RES 阻断显着增强了含紫杉醇纳米颗粒对人类前列腺癌的治疗效果：通过扩散 MRI 检测到给药后 48 小时内大量肿瘤细胞被杀死，并且与单独纳米颗粒治疗相比，实现了显着更长的肿瘤生长延迟。重要的是，RES 阻断不会导致任何体重减轻或肝功能受损，也不会危及 RES 介导的宿主防御。细胞和分子研究揭示了封锁机制，表明这种安全有效的封锁策略具有广泛的用途。 (C) 2014 Elsevier Ltd. 保留所有权利。
Nanoparticles have been intensely pursued for drug delivery for three decades, but their delivery efficiency remains low despite numerous innovations in nanoparticle manufacturing including materials, particle size, surface physicochemistry and targeting moieties. A major reason for this shortfall is their unintended uptake by reticuloendothelial system (RES) in the liver, spleen, Lung, lymph nodes, etc., which competes with the intended targets. Here we demonstrate a temporary blockade of RES by commercial Liposome to substantially delay blood clearance and increase tumor accumulation of small sized, PEGylated nanoparticles. RES-blockade dramatically enhanced therapeutic efficacy of paclitaxel-containing nanoparticles against human prostate cancer: substantial tumor cell kill was detected within 48 h of administration by diffusion MRI and a remarkably longer tumor growth delay was achieved in comparison with nanoparticle treatment alone. Importantly, RES-blockade did not result in any weight loss or impairment of liver function, neither did it jeopardize RES-mediated host defense. Cellular and molecular studies have revealed blockade mechanisms, suggesting this safe and effective blockade strategy has broad utility. (C) 2014 Elsevier Ltd. All rights reserved.