Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles

Abstract

Over the last few decades, nanoparticles have been studied in theranostic field with the objective of exhibiting a long circulation time through the body coupled to major accumulation in tumor tissues, rapid elimination, therapeutic potential and contrast properties. In this context, we developed sub-5 nm gadolinium-based nanoparticles that possess in vitro efficient radiosensitizing effects at moderate concentration when incubated with head and neck squamous cell carcinoma cells (SQ20B). Two main cellular internalization mechanisms were evidenced and quantified: passive diffusion and macropinocytosis. Whereas the amount of particles internalized by passive diffusion is not sufficient to induce in vitro a significant radiosensitizing effect, the cellular uptake by macropinocytosis leads to a successful radiotherapy in a limited range of particles incubation concentration. Macropinocytosis processes in two steps: formation of agglomerates at vicinity of the cell followed by their collect via the lamellipodia (i.e. the "arms") of the cell. The first step is strongly dependent on the physicochemical characteristics of the particles, especially their zeta potential that determines the size of the agglomerates and their distance from the cell. These results should permit to control the quantity of particles internalized in the cell cytoplasm, promising ambitious opportunities towards a particle-assisted radiotherapy using lower radiation doses.

68 Ga-Radiolabeled AGuIX Nanoparticles as Dual-Modality Imaging Agents for PET/MRI-Guided Radiation Therapy

“…In vitro experiments previously published by the team on accumulation in tumors have shown that the NPs are internalized in tumors cells notably by macropinocytosis mechanism [27]. In the vesicles, the NPs are aggregated.…”

Decorated ultrathin bismuth selenide nanosheets as targeted theranostic agents for in vivo imaging guided cancer radiation therapy

“…High-Z elements with larger X-ray interaction cross-sections than light elements (for example, H, O, N and C) could increase the energy deposition and radiolytic hydrolysis in the vicinity of the materials. 2 Several high-Z materials, such as germanium nanoparticles (NPs), 13 iron oxide NPs, 14,15 lanthanidebased compounds, 16 iodine, 17 gold-based NPs 18 and nuclear-targeting gadolinium-based NPs, 19 have recently been used as adjuvants to enhance cellular radiosensitivity. However, few are efficient in in vivo cancer radiotherapy.…”

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells

“…10,41,52 Several different methods can be used to evaluate radiosensitivity in the presence of AuNPs. Some studies used clonogenic assays and multiple doses to construct a survival curve, 41,[53][54][55][56] while others conducted viable cell counting, metabolic assays (enzymatic reduction of tetrazolium dye including MTT, MTS or WST-1) and resazurin sodium salt reduction (Alamar blue test) at a single radiation dose. [57][58][59] Thus, it is difficult to compare our results for radiosensitivity with those of other studies because different cell lines, AuNPs, radiation energy, radiation dosage, evaluation methods and measurement time of cell viability after IR were used.…”