Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems.
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.
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan. ekondo@aichi-cc.jp
Eisaku
E
Kondo
Ken
K
Saito
Yuichi
Y
Tashiro
Kaeko
K
Kamide
Shusei
S
Uno
Tomoko
T
Furuya
Masao
M
Mashita
Kiichiro
K
Nakajima
Tomoyuki
T
Tsumuraya
Naoya
N
Kobayashi
Masahiro
M
Nishibori
Mitsune
M
Tanimoto
Masayuki
M
Matsushita
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D019151:Peptide Library; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D019151:Peptide Library; D034741:RNA, Small Interfering