期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 457, 期 2, 页码 206-212出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.12.089
关键词
CPP; DDS; Peptide; Glioblastoma; Cancer
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Uehara Memorial Foundation
- Takeda Science Foundation
- Special Account Budget for Education and Research from MEXT
- Promotion Project of Medical Clustering of Okinawa prefecture
- Grants-in-Aid for Scientific Research [23390352, 25293048] Funding Source: KAKEN
Cell-penetrating peptides (CPPs) as a novel biomedical delivery system have been highly anticipated, since they can translocate across biological membranes and are capable of transporting their cargo inside live cells with minimal invasiveness. However, non-selective internalization in various cell types remains a challenge in the clinical application of CPPs, especially in cancer treatment. In this study, we attempted to identify novel cancer-homing CPPs to target glioblastoma multiforme (GBM), which is often refractory and resistant to treatment. We screened for CPPs showing affinity for the human GBM cell line, U87MG, from an mRNA display random peptide library. One of the candidate peptides which amino-acid sequence was obtained from the screening showed selective cell-penetrating activity in U87MG cells. Conjugation of the p16(1NK4a) functional peptide to the GBM-selective CPP induced cellular apoptosis and reduced phosphorylated retinoblastoma protein levels. This indicates that the CPP was capable of delivering a therapeutic molecule into U87MG cells inducing apoptosis. These results suggest that the novel CPP identified in this study permeates with high affinity into GBM cells, revealing it to be a promising imaging and therapeutic tool in the treatment of glioblastoma. (C) 2014 Elsevier Inc. All rights reserved.
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