Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

作者：Lu Wang, Yafei Rao, Xiali Liu, Liya Sun, Jiameng Gong, Huasheng Zhang, Lei Shen, Aihua Bao, Hong Yang · 发表于：Journal of Nanobiotechnology · 年份：2021 · DOI：10.1186/s12951-021-00803-w · 被引用次数：52 · 研究领域：Inhalation and Respiratory Drug Delivery、Immune Response and Inflammation、Andrographolide Research and Applications

BACKGROUND: Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. RESULTS: In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthe...