EVALUATING ENDOCRINE AND OXIDATIVE EFFECTS OF POLYLACTIC ACID NANOPLASTICS (PLA-NPs) ON BREAST CELL MODELS

Maria Denise AMICO¹, Antonietta SANTORO², Erwin Pavel LAMPARELLI², Giovanna DELLA PORTA², Magdalena GORSKA-PONIKOWSKA^3,4,5, Francesca RAPPA^1,5, Fabio BUCCHIERI¹, Francesco CAPPELLO^1,5 | ¹Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Italy; ²Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, Italy; ³Department of Medical Chemistry, Medical University of Gdansk, Poland; ⁴Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, Germany; ⁵Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy

Plastic polymers, thanks to their numerous properties, have found widespread use in daily human life, replacing many traditional materials. However, improper disposal and environmental accumulation of plastics have generated serious ecological concerns. Exposure to atmospheric agents causes the fragmentation of plastics into microplastics (MPs) and nanoplastics (NPs), which persist in the environment and, through biomagnification, reach humans. Given the proven hazards of conventional plastics to organisms and the environment, biodegradable polymers such as Polylactic Acid (PLA) have been developed to safeguard the planet and its inhabitants. PLA, promoted as a “green” alternative to conventional plastics, is used in various sectors, from food packaging to biomedical applications, including medical devices and controlled drug delivery systems, thanks to its biocompatibility and perceived safety. However, recent studies have questioned the actual biodegradability of PLA, and the increasing release of MPs and NPs derived from PLA-based materials raises concerns about the biological effects of these particles, particularly as potential endocrine disruptors (EDCs) capable of interfering with hormonal regulation and key processes such as development, reproduction, and metabolism. Previous research has shown that MPs and NPs from standard plastic polymers such as polystyrene, polyethylene, and polypropylene can alter the endocrine system in both in vitro and in vivo models. These findings motivate the investigation of the potential endocrine-disrupting effects of PLA nanoplastics (PLA-NPs). Such evidence provides a strong foundation to explore the endocrine-disrupting potential of PLA-NPs, a biodegradable material widely used in biomedical fields. To date, no systematic studies have evaluated the impact of PLA-NPs on the endocrine system, making this research pioneering in filling a significant knowledge gap. This study aims to evaluate the endocrine and oxidative effects of PLA-NPs on three cell models: MCF-7 (ER-positive breast carcinoma), MDA-MB-231 (triple-negative breast carcinoma), and HB-2 (normal mammary epithelial cells). Cells will be treated with PLA-NPs at concentrations of 50, 100, and 300 µg/mL for 24, 48, and 72 hours. Cell viability (MTT assay) and proliferation (Ki-67 analysis by Western blot and immunofluorescence), reactive oxygen species production (DCFH-DA), lipid peroxidation (MDA assay), and antioxidant enzyme activity (SOD, CAT) will be assessed. The expression of hormone receptors (ERα, ERβ, PR, AR), oxidative stress markers (Nrf2, HO-1), proteins involved in cellular damage (p53), and apoptosis (Bax, Bcl-2, caspase-3) will be analyzed by Western blot and immunofluorescence. The expected results will provide novel insights into the role of PLA-NPs in modulating hormonal signaling and oxidative stress in mammary cells, contributing to a more accurate risk assessment associated with the use of bioplastics in human exposure contexts.

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