Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

Eisaku Kondo (), Ken Saito, Yuichi Tashiro, Kaeko Kamide, Shusei Uno, Tomoko Furuya, Masao Mashita, Kiichiro Nakajima, Tomoyuki Tsumuraya, Naoya Kobayashi, Masahiro Nishibori, Mitsune Tanimoto and Masayuki Matsushita ()
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Eisaku Kondo: Aichi Cancer Center Research Institute
Ken Saito: Aichi Cancer Center Research Institute
Yuichi Tashiro: Okayama University Graduate School of Natural Science and Technology
Kaeko Kamide: Mitsubishi Tanabe Pharma Corporation
Shusei Uno: Mitsubishi Tanabe Pharma Corporation
Tomoko Furuya: Yamaguchi University Graduate School of Medicine
Masao Mashita: Sigma-Aldrich Japan Corporation
Kiichiro Nakajima: KNC Laboratories Co. Ltd.
Tomoyuki Tsumuraya: Graduate School of Medicine, University of the Ryukyus
Naoya Kobayashi: Okayama Saidaiji Hospital
Masahiro Nishibori: Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mitsune Tanimoto: Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Masayuki Matsushita: Graduate School of Medicine, University of the Ryukyus

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: Abstract 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.

Date: 2012
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DOI: 10.1038/ncomms1952

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