암 줄기 세포 검출을 위한 생체적합성 저분자 펩타이드 개발 연구

Abstract

Cancer, also known as a malignant neoplasm, is a group of diseases in which cells change and grow out of control. Technological advance and better understanding of these cancer cell biology can effectively improve the survival rate for nearly all types of cancer. However, the recurrence and metastasis of cancer represent the elaborate obstacles to overcome in the treatment of cancer. Recent studies have supported the cancer stem cells (CSCs) hypothesis, which posits that tumors originate from tissue stem cells or their early progenitors and as a result, produce tumors that retain stem cell properties. CSCs, as a subpopulation of cancer cells, have similar characteristics with human normal stem cell that have the ability for self-renewal, differentiation into various types of cancer cells and extensive proliferation. Although traditional cancer therapies kill and reduce rapidly dividing cancer cells, they may spare CSCs that can then give rise to a new tumor due to the lack of target specificity to elucidate the CSCs. Thus, the diagnosis and determination of prognosis made by CSCs markers could be a key strategy to eradicate CSCs and cure the cancer. In this study, we have initially screened the novel diverse peptides displayed on M13 bacteriophages that binds to CD133, CD44 and PKC δ as CSCs markers with high affinity (picomolar range). Based on a screened peptides, we designed the nanocomplexation and functional peptides to enhance the targeting efficiency towards CSCs markers. The peptide based imaging agent designed in this study exhibited the stimulus responsive fluorescence imaging property wih high accuracy towards CD133 as glioma stem cell marker. Cooperative binding effect of PDPP (Polyvalent Directed Peptide Polymer) successfully enhances the detection sensitivity on CD44 as breast cancer stem cell marker. As an inhibitor, the peptide possesses higher inhibition potency than chemical drug towards PKC δ as glioma stem cell marker. The current study highlights the promising role of small peptides as effective tool for detection the CSCs via active targeting. It is further suggested that the conjugation of identified peptides with the various nanomaterials would enhance their physicochemical stability and thus lead to the CSCs detection system not only accurate targeting the CSCs marker but also cellular imaging property. In brief, identification of small peptide might be a useful strategy in the development of target specific disease diagnostic system.