Selection and identification of novel peptides specifically targeting human cervical cancer

Amino Acids. 2018 May;50(5):577-592. doi: 10.1007/s00726-018-2539-1. Epub 2018 Feb 12.

Abstract

Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer deaths among females in underdeveloped countries. This study aimed to identify several novel cervical cancer-specific targeting peptides (CSPs) to provide new methods for the effective diagnosis and treatment of cervical cancer. Peptide library screening in vivo was performed on human cervical cancer xenografts with Ph.D.™-12 and C7C phage display peptide libraries. Two specific peptide sequences (GDALFSVPLEVY and KQNLAEG), which were enriched in tumors, were screened, and respectively, named CSP-GD and CSP-KQ through three rounds of biopanning. The in vivo tumor-targeting ability of these peptides was identified by injecting them into mice with cervical cancer xenograft. CSPs were compounded and labeled with fluorescein isothiocyanate (FITC). The specificity and affinity of FITC-CSPs were evaluated in human cervical cancer cell lines and tissue microarrays in vitro by immunofluorescent staining. Results showed that FITC-CSP-GD and FITC-CSP-KQ evidently and specifically bound to the cell membrane and cytoplasm of SiHa, ME-180, and C-33A cells in vitro. In human cervical cancer tissue, FITC-CSP-GD and FITC-CSP-KQ strongly targeted human cervical adenocarcinoma and cervical squamous cell carcinoma tissues, respectively. A bright FITC signal was located mainly on the cell membrane and cytoplasm of tumor cells. In conclusion, the novel 12-residue peptide CSP-GD and 7-residue peptide CSP-KQ could specifically target human cervical cancer and may have the potential to be used in the diagnosis and targeted therapy of cervical cancer.

Keywords: Cervical cancer; Peptides; Phage display; Tumor targeting.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Peptide Library*
  • Uterine Cervical Neoplasms* / diagnostic imaging
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Peptide Library