1 DENDRIMER SIZE AND BRAIN TARGETING

Nanotechnologies have demonstrated considerable success in targeting specific tissues and breaching biological barriers for the treatment of various cancers. As such, improving nanoparticle performance through optimization of their physicochemical properties represents one of the most widely investigated topics in preclinical nanotechnology research. In this issue of Bioengineering & Translational Medicine, a team led by Professor Rangaramanujam Kannan from the Center for Nanomedicine, Wilmer Eye Institute at Johns Hopkins School of Medicine, describes a systematic study to determine how dendrimer size affects targeting of brain tumors in vivo. This work utilized two distinct orthotropic and clinically relevant brain tumor models in both mice and rats to show that Generation 6 dendrimers exhibited ~10‐fold higher tumor accumulation at 24 hr as compared to Generation 4 dendrimers. Generation 6 dendrimers were experimentally determined to be ~6.7 nm in diameter whereas Generation 4 dendrimers were ~ 4.3 nm in diameter, an important distinction that was most likely responsible for the significantly enhanced accumulation of the smaller Generation 4 dendrimers in the kidneys over a 48 hr period in both animal models. The authors associated this enhanced kidney accumulation with higher renal clearance and thus less persistence and shorter circulation in the vasculature, thereby limiting opportunities to interact with the brain tumors and decreasing accumulation. This work clearly demonstrates the importance of considering nanoparticle physical properties for their end application by highlighting how an ~2.3 nm difference in diameter could influence accumulation in brain tumors by ~10‐fold.1

中文翻译：

---

BioTM 嗡嗡声（第 5 卷，第 2 期）。

1 树枝状大分子大小和脑靶向

纳米技术在针对特定组织和突破生物屏障治疗各种癌症方面已取得了相当大的成功。因此，通过优化纳米粒子的物理化学性质来提高纳米粒子的性能是临床前纳米技术研究中最广泛研究的主题之一。在本期《生物工程与转化医学》中，由约翰·霍普金斯大学医学院威尔默眼科研究所纳米医学中心的 Rangaramanujam Kannan 教授领导的团队描述了一项系统研究，以确定树枝状大分子的大小如何影响体内脑肿瘤的靶向。这项工作在小鼠和大鼠中使用了两种不同的正交各向异性和临床相关的脑肿瘤模型，结果表明，与第 4 代树枝状聚合物相比，第 6 代树枝状聚合物在 24 小时内的肿瘤积累量高出约 10 倍。经实验确定，第 6 代树枝状聚合物的直径约为 6.7 nm，而第 4 代树枝状聚合物的直径约为 4.3 nm，这是一个重要的区别，很可能是 48 小时内较小的第 4 代树枝状聚合物在肾脏中的积累显着增加的原因两种动物模型中的时期。作者将这种增强的肾脏蓄积与更高的肾脏清除率联系起来，从而减少了血管系统中的持久性和更短的循环，从而限制了与脑肿瘤相互作用的机会并减少了蓄积。这项工作通过强调约 2.3 nm 的直径差异如何影响脑肿瘤中的积累约 10 倍，清楚地证明了考虑纳米粒子物理特性对其最终应用的重要性。 1