Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel.

Abstract

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.

• Authors: Apriliana Cahya Khayrani, Hafizah Mahmud, Aung Ko Ko Oo, Maram H Zahra, Miharu Oze, Juan Du, Md Jahangir Alam, Said M Afify, Hagar A Abu Quora, Tsukasa Shigehiro, Anna Sanchez Calle, Nobuhiro Okada, Akimasa Seno, Koki Fujita, Hiroki Hamada, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 5 (Feb 27 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30818864 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• CD44 protein, human
• Hyaluronan Receptors
• Liposomes
• Paclitaxel

Topics

• Antibodies, Monoclonal (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Glycosylation
• Humans
• Hyaluronan Receptors (metabolism)
• Liposomes (ultrastructure)
• Molecular Targeted Therapy
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Paclitaxel (pharmacology, therapeutic use)