Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
J Control Release. 2021 Apr 10;332:184-193. doi: 10.1016/j.jconrel.2021.02.021. Epub 2021 Feb 24.
In boron neutron capture therapy (BNCT), boron drugs should accumulate selectively within a tumor and be quickly cleared from blood and normal organs. However, it is usually challenging to achieve the efficient tumor accumulation and the quick clearance simultaneously. Here we report the complex composed of a fructose-modified poly(ethylene glycol)-poly(l-lysine) block copolymer and p-boronophenylalanine, termed PEG-P[Lys/Lys(fructose)]-BPA, as a boron delivery system permitting selective accumulation within the target tumor with quick clearance from normal organs as well as blood. Our PEG-P[Lys/Lys(fructose)]-BPA could be internalized into tumor cells through LAT1 amino acid transporter-mediated endocytosis and retain in the targeted cells, thereby accomplishing more efficient accumulation and retention in a subcutaneous tumor than clinically used fructose-BPA complexes. Importantly, the moderately cationic property of the polymer facilitated renal clearance and PEG-P[Lys/Lys(fructose)]-BPA exhibited high accumulation contrast between the target tumor and the blood/normal organ. Finally, upon thermal neutron irradiation, PEG-P[Lys/Lys(fructose)]-BPA significantly inhibited the tumor growth in mice. PEG-P[Lys/Lys(fructose)]-BPA may be a promising boron delivery system for BNCT.
在硼中子俘获治疗（BNCT）中，硼药物应在肿瘤内选择性积累，并迅速从血液和正常器官中清除。然而，通常很难同时实现有效的肿瘤积累和快速清除。在这里，我们报告了一种由果糖修饰的聚乙二醇-聚（赖氨酸）嵌段共聚物和对硼苯丙氨酸组成的复合物，称为 PEG-P[Lys/Lys（果糖）]-BPA，作为一种硼递药系统，允许在目标肿瘤内选择性积累，并从正常器官和血液中快速清除。我们的 PEG-P[Lys/Lys（果糖）]-BPA 可以通过 LAT1 氨基酸转运蛋白介导的内吞作用进入肿瘤细胞，并保留在靶细胞中，从而在皮下肿瘤中实现比临床使用的果糖-BPA 复合物更有效的积累和保留。重要的是，聚合物的中等正电荷性质促进了肾脏清除，PEG-P[Lys/Lys（果糖）]-BPA 表现出靶肿瘤与血液/正常器官之间的高积累对比度。最后，在热中子辐照下，PEG-P[Lys/Lys（果糖）]-BPA 显著抑制了小鼠的肿瘤生长。PEG-P[Lys/Lys（果糖）]-BPA 可能是 BNCT 的一种有前途的硼递药系统。
