title: A novel peptide specifically targeting the vasculature of orthotopic colorectal cancer for imaging detection and drug delivery.
abstract: Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide. Ligand-mediated diagnosis and targeted therapy would have vital clinical applications in cancer treatment. In this study, an orthotopic model of colorectal cancer was established in mice. In vivo phage library selection was then utilized to isolate peptides specifically recognizing the vasculature of colorectal cancer tissues. A phage (termed TCP-1 phage) was isolated by this manner and it homed to the colorectal cancer tissues by 11- to 94-fold more than other organs. Chemical synthetic peptide (CTPSPFSHC, termed TCP-1) displayed by TCP-1 phage inhibited the homing ability of the phage to the tumor mass when co-injected intravenously with the TCP-1 phage into mice with colon cancer. Meanwhile, immunostaining analysis indicated that TCP-1 phage and peptide localized in the vasculature of the colorectal cancer tissue, but not of normal tissues. Moreover, TCP-1 peptide bound to blood vessels of surgical tissue samples of human colorectal cancer. After intravenous injection of FITC-labeled TCP-1 into the tumor-bearing mice for 20h, there was a strong fluorescent signal in the tumors but not other tissues when observed under blue light. In addition, TCP-1 conjugated with a pro-apoptotic peptide specifically induced apoptosis of tumor-associated blood vessels in vivo. The data define a novel peptide TCP-1 as an effective agent for imaging detection and drug delivery for colorectal cancer.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, PR China.
authors.forename: Zhi Jie
authors.initials: ZJ
authors.lastname: Li
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
authors.forename: Simon Siu Man
authors.initials: SS
authors.lastname: Ng
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Li
authors.forename: Clover Ching Man
authors.initials: CC
authors.lastname: Wong
authors.forename: Ya Chun
authors.initials: YC
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Shun Xiang
authors.initials: SX
authors.lastname: Ren
authors.forename: Xue Gang
authors.initials: XG
authors.lastname: Sun
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Chan
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000175:diagnosis* / Q000188:drug therapy; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D019793:Fluorescein / Q000008:administration & dosage; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D019151:Peptide Library; D010455:Peptides; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein