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

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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/immunologyApoptosis/drug effectsCell Line, TumorFemaleGene Expression Regulation, Neoplastic/drug effectsHSP70 Heat-Shock Proteins/chemistry/metabolismHeat-Shock Proteins/chemistry/metabolismHumansMembrane Proteins/chemistry/metabolismMolecular Targeted Therapy/methodsNanoparticles/chemistryNeoplasm InvasivenessOligopeptides/immunologyOvarian Neoplasms/drug therapy/pathologyPaclitaxel/chemistry/pharmacologyProtein Sorting Signals
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PMID: 22713763
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Article (Published version) (610 Kb) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Laboratoire de biologie des tumeurs gynécologiques et du développement (927)
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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

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Deposited on : 2013-12-09

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