Impact of Macrophages on the Interaction of Cetuximab-Functionalized Polyelectrolyte Capsules with EGFR-Expressing Cancer Cells

Abstract

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.

Interaction of Serum and Plasma Proteins with Polyelectrolyte Microparticles with Core/Shell and Shell-Only Structures

“…Calcium carbonate cores were obtained using the coprecipitation reaction in a mixture of equimolar solutions of sodium carbonate and calcium chloride in an aqueous medium containing 1% poly­(vinyl alcohol) and 0.05% methylcellulose (PVA/MC) as a thickening agent . First, 15 mL of a PVA/MC solution was added to 7.5 mL of 0.33 M CaCl 2 and mixed using an UltraTurrax T 25 digital dispersing device (IKA-Werke GmbH & Co. KG, Germany) at 5000 rpm until a homogeneous medium was obtained.…”

“…Calcium carbonate cores were obtained using the coprecipitation reaction in a mixture of equimolar solutions of sodium carbonate and calcium chloride in an aqueous medium containing 1% poly(vinyl alcohol) and 0.05% methylcellulose (PVA/MC) as a thickening agent. 29 First, 15 mL of a PVA/MC solution was added to 7.5 mL of 0.33 M CaCl 2 and mixed using an UltraTurrax T 25 digital dispersing device (IKA-Werke GmbH & Co. KG, Germany) at 5000 rpm until a homogeneous medium was obtained. After that, 7.5 mL of Na 2 CO 3 was added, and the final mixture was vigorously agitated at 15,000 rpm for 30 s. The resulting suspension was transferred to a 50 mL test tube, Milli-Q water was added to a volume of 50 mL, and the suspension was centrifuged.…”

Cytotoxic Effects of Doxorubicin on Cancer Cells and Macrophages Depend Differently on the Microcarrier Structure

“…Core/shell microparticles consisting of the MBs coated with eight-layer polymer shells (MB(+8L)) and MC consisting of the polymer shell alone (MC(8L)) were obtained by means of layer-by-layer adsorption of oppositely charged polyelectrolytes (the polycation PAH and the polyanion PSS) onto the MB surface [22,23,31]. About 10 8 MBs, dried after the synthesis, were resuspended in 0.5 mL of ultrapure water.…”

“…Optimal selection of the physicochemical properties of microstructures, such as their shape, size, and structure (the number of polymer layers in the shell, the presence or absence of a core, integration of other functional components, etc.) [ 23 ], can contribute to a prolonged release of the antitumor agent [ 19 , 24 , 25 ], an increased time of its circulation in the body, and decreased side effects on healthy tissues and organs [ 26 ], as well as ensure its targeted delivery to the tumor site without loss of its pharmacological properties [ 27 ].…”

Interaction of Human Serum and Plasma Proteins with Polyelectrolyte Microcapsules of Different Structures

“…Calcium carbonate cores were obtained using the co-precipitation reaction in a mixture of equimolar solutions of sodium carbonate and calcium chloride in an aqueous medium containing 1% polyvinyl alcohol and 0.05% methylcellulose (PVA/MC) as a thickening agent 29 . First, 15 mL of a PVA/MC solution was added to 7.5 mL of 0.33 M CaCl2 and mixed using an UltraTurrax® T 25 digital dispersing device (IKA®-Werke GmbH & Co. KG, Germany) at 5000 rpm until a homogeneous medium was obtained.…”