Temporary suppression the sequestrated function of host macrophages for better nanoparticles tumor delivery.
Temporary suppression the sequestrated function of host macrophages for better nanoparticles tumor delivery.
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DOI：
10.1080/10717544.2018.1474965
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Hao J;Han T;Wang M;Zhuang Q;Wang X;Liu J;Wang Y;Tang H
通过纳米粒的修饰实现靶向给药已成为抗肿瘤药物高效给药的主流。然而，低递送效率成为癌症纳米药物临床转化的最大障碍，因为它们中的大多数被隔离在肝脏中，其中更多的巨噬细胞负责捕获全身施用的纳米颗粒。在这项研究中，我们发现肝脏巨噬细胞的消耗可以导致纳米颗粒递送的上级改善。首先，我们开发了含氯膦酸盐的脂质体（clodrolip），以短暂抑制巨噬细胞的吞噬功能，预先用clodrolip处理小鼠时，肝脏中残留的巨噬细胞仅占不到1%。此外，紫杉醇-聚（乳酸-羟基乙酸共聚物）（PTX-PLGA）纳米粒治疗的药代动力学结果显示，巨噬细胞耗竭组中PTX的AUC增加了2.11倍。这些结果意味着去除巨噬细胞将减少纳米颗粒在肝脏中的积累，并改善纳米颗粒递送系统的生物分布和生物利用度。此外，clodrolip和PTX-PLGA纳米粒联合治疗小鼠黑色素瘤导致抗肿瘤功效提高，肿瘤抑制率接近80%。此外，这些组合方案已证明在不良反应发生率方面的毒性可忽略不计。总之，这项研究的令人鼓舞的结果激发了一种合理的策略的产生，专注于微环境引发调节先天免疫和提高纳米颗粒的递送效率。
Orchestration of nanoparticles to achieve targeting has become the mainstream for efficient delivery of antitumor drugs. However, the low delivery efficiency becomes the biggest barrier for clinical translation of cancer nanomedicines, as most of them are sequestrated in the liver where more macrophages located in are responsible for capture of systemic administrated nanoparticles. In this study, we found that the depletion of the liver macrophages could lead to a superior improvement in the nanoparticles delivery. Firstly, we developed clodronate-containing liposomes (clodrolip) to transiently suppress the phagocytic function of macrophages, the residual macrophages in liver only accounted for less than 1% when the mice were treated with clodrolip in advance. In addition, the pharmacokinetics results of treatment with paclitaxel-poly(lactic-co-glycolic acid) (PTX-PLGA) nanoparticles disclosed that the AUC of PTX in the macrophages depletion group increased 2.11-fold. These results meant that the removal of macrophages would decrease the nanoparticles accumulation in the liver and better the biodistribution and bioavailability of nanoparticles delivery systems. Moreover, treatment of mice with melanoma by the combination of clodrolip and PTX-PLGA nanoparticles resulted in an elevated anti-tumor efficacy, the tumor inhibition ratio was nearly reached to 80%. Furthermore, these combinatorial regimens have demonstrated negligible toxicity in incidence of adverse effects. In conclusion, the encouraging results from this study inspire the generation of a rational strategy to focus on microenvironmental priming for modulation of innate immunity and to improve delivery efficiency of nanoparticles.
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影响因子：
2
作者：
Hatakeyama, Hiroto;Akita, Hidetaka;Harashima, Hideyoshi
通讯作者：
Harashima, Hideyoshi
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H
DOI：
10.1007/978-1-60327-360-2_13
发表时间：
2010-01-01
期刊：
LIPOSOMES: METHODS AND PROTOCOLS, VOL 1
影响因子：
--
作者：
van Rooijen, Nico;Hendrikx, Esther
通讯作者：
Hendrikx, Esther
影响因子：
6
作者：
Radi, Zaher A.;Koza-Taylor, Petra H.;Sadis, Seth
通讯作者：
Sadis, Seth