目前，多形性胶质母细胞瘤（GBM）是最常见、最恶性的脑肿瘤，尚无有效的治疗方法。血脑（肿瘤）屏障（BB（T）B）由紧密连接的内皮细胞和周细胞（部分脉管系统塌陷）组成，阻碍纳米药物在肿瘤组织中的积累。我们的目的是探讨纳米药物尺寸对 GBM 被动靶向的影响。构建了一系列尺寸可调的聚乙二醇 (PEG) 接枝共聚物 (gPEG)，其流体动力学直径为 8-30 nm。使用原位脑肿瘤小鼠进行的生物分布研究表明，gPEG 脑肿瘤累积在 10 nm 处达到最大，约 14 剂量%/g 肿瘤，比正常脑区域高 19 倍，比 30 脑区域高 4.2 倍。 -纳米gPEG。值得注意的是，由于 gPEG 的长期血液循环特性（源自密集的 PEG 堆积结构），10 nm gPEG 表现出比 11 nm 线性 PEG 更高的脑肿瘤积累。 10 nm gPEG 比较大的 gPEG (>10 nm) 更深入地渗透到脑肿瘤组织中。这项研究首次证明了用于被动 GBM 靶向的纳米医学缩小策略的巨大潜力。

Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood-brain (tumor) barrier (BB(T)B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedicine accumulation in tumor tissues. We aimed to explore the effect of nanomedicine size on passive targeting of GBM. A series of size-tunable poly(ethylene glycol) (PEG)-grafted copolymers (gPEGs) were constructed with hydrodynamic diameters of 8-30 nm. Biodistribution studies using orthotopic brain tumor-bearing mice revealed that gPEG brain tumor accumulation was maximized at 10 nm with ∼14 dose %/g of tumor, which was 19 times higher than that in the normal brain region and 4.2 times higher than that of 30-nm gPEG. Notably, 10-nm gPEG exhibited substantially higher brain tumor accumulation than 11-nm linear PEG owing to the prolonged blood circulation property of gPEGs, which is derived from a densely PEG-packed structure. 10 nm gPEG exhibited deeper penetration into the brain tumor tissue than the larger gPEGs did (>10 nm). This study demonstrates, for the first time, the great potential of a nanomedicine downsizing strategy for passive GBM targeting.