Molecular targeting of neuroblastoma with a novel p16INK4a transporter system.
Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists in vivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.
Department of Neurosurgery, Kansai Medical University, Moriguchi City, Osaka 570-8507, Japan.
Takuya
T
Kawaguchi
Second Department of Pathology, Aichi Medical University School of Medicine, Yazago, Nagakute City, Aichi 480-1195, Japan.
Kazuhiro
K
Yoshikawa
Higashi Oosakayamaji Hospital, Higashiosaka City, Osaka 578-0925, Japan.
Keiji
K
Kawamoto
Department of Neurosurgery, Kansai Medical University, Hirakata City, Osaka 573-1191, Japan.
Kunikazu
K
Yoshimura
Department of Neurosurgery, Kansai Medical University, Hirakata City, Osaka 573-1191, Japan.
Hideyuki
H
Oshige
Department of Neurosurgery, Kansai Medical University, Hirakata City, Osaka 573-1191, Japan.
Akio
A
Asai
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000138:chemical synthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods*; D009374:Neoplasms, Experimental; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D051381:Rats; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010455:Peptides; D016160:Retinoblastoma Protein; C000593382:Wr-T peptide