| Autor: |
Nifontova G; Laboratoire de Recherche en Nanosciences, LRN-EA4682, Université de Reims Champagne-Ardenne, 51096 Reims, France., Kalenichenko D; Laboratoire de Recherche en Nanosciences, LRN-EA4682, Université de Reims Champagne-Ardenne, 51096 Reims, France., Kriukova I; Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russian Federation.; Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russian Federation., Terryn C; Plateau Technique PICT, Université de Reims Champagne-Ardenne, 51096 Reims, France., Audonnet S; URCACyt, Flow Cytometry Technical Platform, Université de Reims Champagne-Ardenne, 51096, Reims, France., Karaulov A; Sechenov First Moscow State Medical University, Sechenov University, 119146 Moscow, Russian Federation., Nabiev I; Laboratoire de Recherche en Nanosciences, LRN-EA4682, Université de Reims Champagne-Ardenne, 51096 Reims, France.; Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russian Federation.; Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russian Federation.; Sechenov First Moscow State Medical University, Sechenov University, 119146 Moscow, Russian Federation., Sukhanova A; Laboratoire de Recherche en Nanosciences, LRN-EA4682, Université de Reims Champagne-Ardenne, 51096 Reims, France. |
| Abstrakt: |
Polyelectrolyte capsules (PCs) are a promising tool for anticancer drug delivery and tumor targeting. Surface functionalization of PCs with antibodies is widely used for providing their specific interactions with cancer cells. The efficiency of PC-based targeted delivery systems can be affected by the cellular heterogeneity of the tumor, particularly by the presence of tumor-associated macrophages. We used human epidermoid carcinoma cells and macrophages derived from human leukemia monocytic cells in either monoculture or coculture to analyze the targeting capacity and internalization efficiency of PCs with a mean size of 1.03 ± 0.11 μm. The PCs were functionalized with the monoclonal antibody cetuximab targeting the human epidermal growth factor receptor (EGFR). We have shown that surface functionalization of the PCs with cetuximab ensures a specific interaction with EGFR-expressing cancer cells and promotes capsule internalization. In monoculture, the macrophages derived from human leukemia monocytic cells have been found to internalize both nonfunctionalized PCs and cetuximab-functionalized PCs (Cet-PCs) more intensely compared to epidermoid carcinoma cells. The internalization of Cet-PCs by cancer cells is mediated by lipid rafts of the cell membrane, whereas the PC internalization by macrophages is only slightly influenced by lipid rafts. Experiments with a coculture of human epidermoid carcinoma cells and macrophages derived from human leukemia monocytic cells have shown that Cet-PCs preferentially interact with cancer cells, which are subsequently attacked by macrophages. These data can be used to further improve the strategy of PC functionalization for targeted delivery, with the cellular heterogeneity of the tumor microenvironment taken into consideration. |
