Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles

BackgroundInorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution. Method/Principal FindingsUsing a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum. ConclusionNeutral and zwitterionic nanoparticles demonstrated longer circulation time via both IP and IV administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting.**背景**：无机纳米颗粒（inorganic nanoparticles）为包括检测、诊断与治疗在内的生物医学应用提供了极具潜力的工具。尽管电荷等表面性质被认为对其体内行为具有重要影响，但目前关于纳米颗粒表面化学如何调控其药代动力学、肿瘤摄取与生物分布的相关研究仍十分匮乏。 **方法与主要发现**：本研究使用一系列结构同源的纳米颗粒，以中性（TEGOH）、两性离子（Tzwit）、负电性（TCOOH）及正电性（TTMA）纳米颗粒为研究对象，探究了表面电荷对包括肿瘤摄取与生物分布在内的药理学特性的影响。实验中，我们分别通过尾静脉或腹膜内注射途径，将纳米颗粒注入正常小鼠与无胸腺（athymic）小鼠体内。 **结论**：经腹腔注射（IP）与静脉注射（IV）给药后，中性与两性离子纳米颗粒均展现出更长的循环时长；而负电性与正电性纳米颗粒的半衰期相对较短。上述药理学特征在对应纳米颗粒的肿瘤摄取与生物分布中得到了充分体现，其中中性与两性离子纳米颗粒可通过被动靶向实现更高效的肿瘤摄取。