The propensity of the hepatic macrophages (Kupffer cells) to rapidly intercept particulate materials from the blood has been frustrating in redirecting intravenously injected nanomedicines to pathological sites in sufficient quantities to exert appropriate pharmacological effect. The development of long circulating nanoparticles has offered unprecedented opportunities for controlled drug release within vasculature and for drug delivery to sites other than Kupffer cells. These developments were based on mechanistic understanding of complex and integrated body’s defences against intruders as well as translation of protective strategies developed by the body’s own cells and virulent pathogens against immune attack. Thanks to interdisciplinary and integrated approaches, numerous organic and inorganic nanoparticles with long circulating properties have become available. By long circulation we mean particles that remain in the blood for periods of hours rather than minutes, but blood longevity must be tuned in accordance with therapeutic needs. Here, we provide a brief history of these efforts and highlight important lessons learned in camouflaging nanoparticles with strategies that avoid rapid interception by Kupffer cells.

肝巨噬细胞（Kupffer 细胞）快速拦截血液中颗粒物质的倾向一直阻碍着将静脉注射的纳米药物以足够的量重定向到病理部位以发挥适当的药理作用。长循环纳米颗粒的发展为控制药物在脉管系统内的释放和药物递送至库普弗细胞以外的部位提供了前所未有的机会。这些发展是基于对复杂和综合的身体抵御入侵者的防御机制的理解，以及对身体自身细胞和毒性病原体针对免疫攻击开发的保护策略的翻译。多亏了跨学科和综合方法，许多具有长循环特性的有机和无机纳米粒子已经可用。我们所说的长循环是指颗粒在血液中保留数小时而不是数分钟，但血液寿命必须根据治疗需要进行调整。在这里，我们提供了这些努力的简要历史，并强调了在使用避免库普弗细胞快速拦截的策略伪装纳米粒子时学到的重要经验教训。