单核吞噬细胞系统
纳米载体
氯喹
体内分布
巨噬细胞
药物输送
脂质体
纳米医学
药理学
内吞作用
靶向给药
药品
医学
化学
免疫学
疟疾
纳米技术
纳米颗粒
受体
材料科学
生物化学
内科学
体外
有机化学
作者
Joy Wolfram,Sara Nizzero,Haoran Liu,Feng Li,Guodong Zhang,Li Zheng,Haifa Shen,Elvin Blanco,Mauro Ferrari
标识
DOI:10.1038/s41598-017-14221-2
摘要
Abstract Site-specific localization is critical for improving the therapeutic efficacy and safety of drugs. Nanoparticles have emerged as promising tools for localized drug delivery. However, over 90% of systemically injected nanocarriers typically accumulate in the liver and spleen due to resident macrophages that form the mononuclear phagocyte system. In this study, the clinically approved antimalarial agent chloroquine was shown to reduce nanoparticle uptake in macrophages by suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of chloroquine substantially decreased the accumulation of liposomes and silicon particles in the mononuclear phagocyte system and improved tumoritropic and organotropic delivery. The novel use of chloroquine as a macrophage-preconditioning agent presents a straightforward approach for addressing a major barrier in nanomedicine. Moreover, this priming strategy has broad applicability for improving the biodistribution and performance of particulate delivery systems. Ultimately, this study defines a paradigm for the combined use of macrophage-modulating agents with nanotherapeutics for improved site-specific delivery.
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