A549 Alveolar Carcinoma Spheroids as a Cytotoxicity Platform for Carboxyl- and Amine-Polyethylene Glycol Gold Nanoparticles.

Autor: Petzer M; Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa., Fobian SF; Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa., Gulumian M; Molecular Medicine and Haematology, School of Pathology, University of Witwatersrand, Johannesburg, South Africa.; Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa., Steenkamp V; Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa., Cordier W; Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Jazyk: angličtina
Zdroj: Pharmacology research & perspectives [Pharmacol Res Perspect] 2025 Feb; Vol. 13 (1), pp. e70051.
DOI: 10.1002/prp2.70051
Abstrakt: Gold nanoparticles (AuNPs) present with unique physicochemical features and potential for functionalization as anticancer agents. Three-dimensional spheroid models can be used to afford greater tissue representation due to their heterogeneous phenotype and complex molecular architecture. This study developed an A549 alveolar carcinoma spheroid model for cytotoxicity assessment and mechanistic evaluation of functionalized AuNPs. A549 spheroids were generated using an agarose micro-mold and were characterized (morphology, acid phosphatase activity, protein content) over 21 culturing days. The 72-h cytotoxicity of carboxyl-polyethylene glycol- (PCOOH-) and amine-polyethylene glycol- (PNH 2 -) functionalized AuNPs against Day 7 spheroids was assessed by determining spheroid morphology, acid phosphatase activity, protein content, caspase-3/7 activity, and cell cycle kinetics. Spheroids remained stable over the experimental period. Although the A549 spheroids' volume increased while remaining viable over the culturing period, structural integrity decreased from Day 14 onwards. The PCOOH-AuNPs lacked cytotoxicity at a maximum concentration of 1.2 × 10 12 nanoparticles/mL with no prominent alteration to the cellular processes investigated, while the PNH 2 -AuNPs (at a maximum of 4.5 × 10 12 nanoparticles/mL) displayed dose- and time-dependent cytotoxicity with associated loss of spheroid compactness, debris formation, DNA fragmentation, and a 75% reduction in acid phosphatase activity. Differentiation between cytotoxic and non-cytotoxic AuNPs was achieved, with preliminary elucidation of cytotoxicity endpoints. The PNH 2 -AuNPs promote cytotoxicity by modulating cellular kinetics while destabilizing the spheroid ultrastructure. The model serves as a proficient platform for more in-depth elucidation of NP cytotoxicity at the preclinical investigation phase.
(© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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