title: Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer.
abstract: Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future.
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
authors: Yao-An
authors: YA
authors: Shen
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Chang-Sheng
authors: CS
authors: Liu
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Yen-Hou
authors: YH
authors: Chang
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Po-Hung
authors: PH
authors: Chen
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Chun-Lin
authors: CL
authors: He
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan. Electronic address: hcw0928@gate.sinica.edu.tw.
authors: Han-Chung
authors: HC
authors: Wu
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cmjuang@yahoo.com.tw.
authors: Chi-Mu
authors: CM
authors: Chuang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D006801:Humans; D008081:Liposomes; D008819:Mice, Nude; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D019151:Peptide Library; D010455:Peptides; D004317:Doxorubicin
keywords: Active targeting; Nanomedicine; Ovarian cancer; Phage display