Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems
Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems
复制标题
DOI：
10.1038/ncomms1952
复制
发表时间：
2012-07-01
影响因子：
16.6
通讯作者：
Matsushita, Masayuki
中科院分区：
文献类型：
--
作者：
Kondo, Eisaku;Saito, Ken;Matsushita, Masayuki
细胞穿透肽因其在非侵入性递送系统中的前景而受到关注。在已鉴定的细胞穿透肽中，TAT 肽已优先用于转导至不同来源的细胞中。然而，这种活性在肿瘤细胞和非肿瘤细胞之间是非选择性的。在这里，我们描述了人工细胞穿透肽，它们根据其谱系选择性且有效地掺入人类肿瘤细胞中。通过信使RNA展示技术构建的随机肽库筛选，获得了10种具有代表性的肿瘤谱系归巢细胞穿透肽，其中一些分离物还经过氨基酸取代进一步修饰。它们有利的肿瘤细胞靶向能力在用于转移性异种植物肿瘤成像和生长抑制的体内小鼠模型中得到证实。这些细胞穿透肽可能有助于以肿瘤起源依赖性方式有效靶向人类肿瘤，并为基于肽的抗肿瘤技术的开发提供框架。
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.