Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer

Yao-An Shen, Chang-Sheng Liu, Yen-Hou Chang, Po-Hung Chen, Chun-Lin He, Han-Chung Wu, Chi-Mu Chuang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalCancer Letters
Volume360
Issue number1
DOIs
Publication statusPublished - Apr 28 2015
Externally publishedYes

Fingerprint

Nanomedicine
Ovarian Neoplasms
Carcinoma
Peptides
Nanoparticles
Peptide Library
Therapeutics
Endocytosis
Drug Resistance
Pharmaceutical Preparations
Bacteriophages
Neoplasms
Clone Cells
liposomal doxorubicin
Ovarian epithelial cancer

Keywords

  • Animals
  • Antibiotics, Antineoplastic/administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Surface Display Techniques
  • Chemistry, Pharmaceutical
  • Doxorubicin/administration & dosage
  • Endocytosis
  • Female
  • Humans
  • Liposomes
  • Mice, Nude
  • Nanomedicine/methods
  • Nanoparticles
  • Neoplasms, Glandular and Epithelial/drug therapy
  • Ovarian Neoplasms/drug therapy
  • Peptide Library
  • Peptides/chemistry
  • Protein Binding
  • Reproducibility of Results
  • Time Factors
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Cite this

Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer. / Shen, Yao-An; Liu, Chang-Sheng; Chang, Yen-Hou; Chen, Po-Hung; He, Chun-Lin; Wu, Han-Chung; Chuang, Chi-Mu.

In: Cancer Letters, Vol. 360, No. 1, 28.04.2015, p. 39-47.

Research output: Contribution to journalArticle

Shen, Yao-An ; Liu, Chang-Sheng ; Chang, Yen-Hou ; Chen, Po-Hung ; He, Chun-Lin ; Wu, Han-Chung ; Chuang, Chi-Mu. / Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer. In: Cancer Letters. 2015 ; Vol. 360, No. 1. pp. 39-47.
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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.",
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AU - He, Chun-Lin

AU - Wu, Han-Chung

AU - Chuang, Chi-Mu

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N2 - 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.

AB - 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.

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