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

被引：11

作者：

Delie, Florence ^{[1
]}

Ribaux, Pascale ^{[2
]}

Petignat, Patrick ^{[2
]}

Cohen, Marie ^{[2
]}

机构：

[1] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, CH-1211 Geneva 4, Switzerland

[2] Univ Hosp Geneva, Dept Obstet & Gynecol, CH-1211 Geneva, Switzerland

来源：

BIOCHIMIE | 2012年 / 94卷 / 11期

关键词：

Nanoparticle; Targeting; Ovarian cancer; GRP78; GRP94; PEPTIDIC GRP78 LIGAND; GLUCOSE-REGULATED PROTEINS; COOH-TERMINAL DOMAIN; CELL-SURFACE GRP78; ENDOPLASMIC-RETICULUM; STRESS INDUCTION; DRUG-DELIVERY; APOPTOSIS; CHAPERONE; RECEPTOR;

D O I：

10.1016/j.biochi.2012.06.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：2391 / 2397

页数：7

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