Institute for Chemical Research, Kyoto University, Kyoto 611-0011, Japan.
J Control Release. 2012 Apr 30;159(2):181-8. doi: 10.1016/j.jconrel.2012.01.016. Epub 2012 Jan 21.
We investigated the biodistribution of arginine-rich cell-penetrating peptides (CPPs) in tumor-xenografted nude mice after intravenous injection of fluorescently labeled CPPs using in vivo imaging. The CPPs used included HIV-1 Tat (48-60), penetratin, and the L- and D-enantiomers of oligoarginines (8, 12, and 16 residues), all of which are reported to have high cell penetration. Among the tested peptides, high accumulation in tumors was observed for the D-form of octaarginine (r8), and glycosaminoglycans played a key role. Injection of an r8-doxorubicin conjugate (4mg doxorubicin/kg) effectively suppressed tumor proliferation, with no significant decrease in mouse weight, whereas administration of doxorubicin itself (6mg/kg), yielding a similar degree of tumor-growth suppression, resulted in significant weight loss. These results suggest the potential of r8 as a prototypic tumor-targeting vector.
我们通过活体成像技术研究了静脉注射荧光标记的富含精氨酸的细胞穿透肽（CPPs）后，CPPs 在肿瘤异种移植裸鼠体内的分布情况。所用的 CPP 包括 HIV-1 Tat（48-60）、Penetratin 以及寡精氨酸的 L-和 D-对映体（8、12 和 16 个残基），这些 CPP 均报道具有较高的细胞穿透能力。在测试的肽中，八聚精氨酸（r8）的 D-形式在肿瘤中有较高的蓄积，糖胺聚糖起着关键作用。注射 r8-阿霉素缀合物（4mg 阿霉素/公斤）可有效抑制肿瘤增殖，而小鼠体重无明显下降，而给予阿霉素本身（6mg/公斤），虽然也能达到相似程度的肿瘤生长抑制，但导致明显的体重下降。这些结果表明 r8 具有作为典型的肿瘤靶向载体的潜力。
