Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?

Abstract

The purpose of this study was to target ovarian cancer cells by coupling paclitaxel (Tx)-loaded nanoparticles (NPs-Tx) to antibodies against KDEL sequence, able to recognize GRP94 and GRP78 that are located at cell surface in cancer cells whereas they are in the endoplasmic reticulum in healthy cells. Tx-loaded poly (DL-lactic acid) nanoparticles coated with anti-KDEL antibodies (NPs-Tx-KDEL) were successfully prepared and characterized. Interaction between tumor cells and NPs-Tx or NPs-Tx-KDEL was observed by microscopy with fluorescently labeled NPs and the efficacy of the different formulations was compared by a viability assay. Particles functionalized with monoclonal antibodies (mAb) showed a higher binding to the cells even though the internalization rate appeared limited. The effect of NPs-Tx-KDEL on cell viability (proliferation) was compared to Tx, NPs, NPs-Tx, anti-KDEL mAb or anti-KDEL mAb in combination with NPs-Tx in Bg-1 ovarian cell line. Our data indicate that NPs-Tx-KDEL significantly increase sensitivity of Bg-1 cells to Tx compared to other treatments. This study confirms the interest of anti-cancer therapy by targeting cell surface GRP78 and GRP94 on cancer cells, and demonstrates the efficiency of coupling KDEL antibodies to NPs.

• Authors: Florence Delie, Pascale Ribaux, Patrick Petignat, Marie Cohen
• Journal: Biochimie (Biochimie) Vol. 94 Issue 11 Pg. 2391-7 (Nov 2012) ISSN: 1638-6183 [Electronic] France
• PMID: 22713763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Endoplasmic Reticulum Chaperone BiP
• HSP70 Heat-Shock Proteins
• HSPA5 protein, human
• Heat-Shock Proteins
• Membrane Proteins
• Oligopeptides
• Protein Sorting Signals
• glucose-regulated proteins
• lysyl-aspartyl-glutamyl-leucine
• Paclitaxel

Topics

• Antibodies, Monoclonal (chemistry, immunology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Endoplasmic Reticulum Chaperone BiP
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• HSP70 Heat-Shock Proteins (chemistry, metabolism)
• Heat-Shock Proteins (chemistry, metabolism)
• Humans
• Membrane Proteins (chemistry, metabolism)
• Molecular Targeted Therapy (methods)
• Nanoparticles (chemistry)
• Neoplasm Invasiveness
• Oligopeptides (immunology)
• Ovarian Neoplasms (drug therapy, pathology)
• Paclitaxel (chemistry, pharmacology)
• Protein Sorting Signals