Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?
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.
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Florence
F
Delie
Pascale
P
Ribaux
Patrick
P
Petignat
Marie
M
Cohen
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D021382:Protein Sorting Signals
D000911:Antibodies, Monoclonal; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D021382:Protein Sorting Signals; C018551:glucose-regulated proteins; C073762:lysyl-aspartyl-glutamyl-leucine; D017239:Paclitaxel