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Ingestion, fate, and impact of micro-, nano-plastics to living cells Ali Can (361237) PUREID: 667695129 Micro- and nanoplastics (MNPs) polystyrene (PS) biodegradable plastics polylactic acid (PLA) polycaprolactone (PCL) cytotoxicity mitochondrial dysfunction oxidative stress high content analysis (HCA) O-PTIR spectroscopy transcriptomics human cell models <p>Micro- and nanoplastics (MNPs),including both conventional and biodegradable polymers, are now widely detectedin environmental matrices and human biological systems, raising concerns abouttheir potential health impacts. Owing to their small size, MNPs can crossbiological barriers, accumulate in organs, and interact with cellularstructures. This thesis investigates the toxicological effects of MNPs,focusing on the influence of polymer type, particle size, and exposureconcentration, using human intestinal (Caco-2), hepatic (HepG2), and neuronal(SH-SY5Y) cell models.</p><p>Experimental studies withpolystyrene (PS) particles (30 nm, 100 nm, and 1.1 μm) demonstrated clear size-and cell-type-dependent toxicity. High Content Analysis revealed that smallerPS nanoparticles induced mitochondrial dysfunction, oxidative stress, andapoptotic responses, particularly in HepG2 and SH-SY5Y cells, while Caco-2cells showed limited sensitivity. O-PTIR spectroscopy identified localisedlipid accumulation and structural reorganisation following PS exposure,indicating disruption of cellular homeostasis. Transcriptomic analyses furthershowed alterations in genes involved in mitochondrial function, apoptosis,autophagy, and inflammation, with low-dose exposure eliciting adaptiveresponses and higher doses triggering pro-inflammatory and pro-apoptoticpathways.</p><p>The toxicity of biodegradablepolymers was also assessed using nano-sized polylactic acid (PLA) andpolycaprolactone (PCL). PLA significantly reduced cell viability across allcell lines, with the strongest effects observed in neuronal cells, whereas PCLeffects were largely confined to SH-SY5Y cells. PLA additionally alteredmitochondrial parameters, indicating cellular stress comparable to that inducedby conventional plastics, highlighting that biodegradability does notnecessarily equate to biological safety.</p><p>Overall, this thesis demonstratesthat MNPs, regardless of polymer type, can induce concentration-, size-, andcell-specific cytotoxic effects associated with mitochondrial dysfunction,oxidative stress, and inflammatory signalling. By integrating cytotoxic,spectroscopic, and transcriptomic approaches, this work provides mechanisticinsight into MNP-induced cellular disruption and contributes to improvedassessment of potential human health risks associated with plastic pollution.</p><br><i>Thesis is embargoed until 31 July 2029.</i> 2026-10-01T16:09:54Z Text Thesis 10.17034/32826212.v1 https://figshare.com/articles/thesis/Ingestion_fate_and_impact_of_micro-_nano-plastics_to_living_cells/32826212 All Rights Reserved Open Access after 2029-07-31