Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
Nat Commun. 2012 Jul 17;3:951. doi: 10.1038/ncomms1952.
Cell-penetrating peptides have gained attention owing to their promise in noninvasive delivery systems. Among the identified cell-penetrating peptides, the TAT peptide has been preferentially used for transduction into cells of diverse origins. However, this activity is nonselective between neoplastic and non-neoplastic cells. Here we describe artificial cell-penetrating peptides that are selectively and efficiently incorporated into human tumour cells, according to their lineage. Ten representative tumour lineage-homing cell-penetrating peptides were obtained by screening of a random peptide library constructed using messenger RNA display technology, and some of the isolates were further modified by amino-acid substitution. Their advantageous tumour cell-targeting ability is corroborated in an in vivo mouse model for imaging and growth suppression of metastatic xenoplant tumours. These cell-penetrating peptides are potentially useful for the efficient targeting of human neoplasms in a tumour origin-dependent manner, and provide a framework for the development of peptide-based anti-tumour technologies.
细胞穿透肽因其在非侵入性递药系统中的应用前景而受到关注。在已鉴定的细胞穿透肽中，TAT 肽优先用于转导多种来源的细胞。然而，这种活性在肿瘤细胞和非肿瘤细胞之间没有选择性。在这里，我们根据细胞谱系描述了人工细胞穿透肽，这些肽可选择性和有效地进入人类肿瘤细胞。通过使用信使 RNA 显示技术构建的随机肽文库筛选获得了 10 个代表性的肿瘤谱系归巢细胞穿透肽，并且一些分离物通过氨基酸取代进一步修饰。在用于成像和抑制转移性异种移植肿瘤生长的体内小鼠模型中证实了它们具有有利的肿瘤细胞靶向能力。这些细胞穿透肽可能有助于以依赖肿瘤起源的方式有效地靶向人类肿瘤，并为基于肽的抗肿瘤技术的发展提供了框架。
