Article (Published version) (610 Kb) - Limited access to UNIGE
Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?
|Published in||Biochimie. 2012, vol. 94, no. 11, p. 2391-7|
|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.|
|Keywords||Antibodies, Monoclonal/chemistry/immunology — Apoptosis/drug effects — Cell Line, Tumor — 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|
|Research group||Laboratoire de biologie des tumeurs gynécologiques et du développement (927)|
|DELIE SALMON, Florence et al. Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?. In: Biochimie, 2012, vol. 94, n° 11, p. 2391-7. https://archive-ouverte.unige.ch/unige:31910|