Biological Modulation of Autophagy by Nanoplastics: A Current Overview

Abstract

Nanoplastics (NPs), an emerging class of environmental pollutants, are increasingly recognized for their potential to interfere with critical cellular processes. Autophagy, a conserved degradative pathway essential for maintaining cellular homeostasis and adaptation to stress, has recently become a focal point of nanotoxicology research. This review synthesizes current evidence on the interactions between NPs and autophagic pathways across diverse biological systems. Findings indicate that NPs can trigger autophagy as an early cellular response; however, prolonged exposure may lead to autophagic dysfunction, contributing to impaired cell viability and disrupted signaling. Particular attention is given to the physiochemical properties of NPs such as size, surface charge, and polymer type, which influence cellular uptake and intracellular trafficking. We also highlight key mechanistic pathways, including oxidative stress and mTOR modulation. Notably, most available studies focus almost exclusively on polystyrene (PS)-based NPs, with limited data on other types of polymers, and several reports lack comprehensive assessment of autophagic flux or downstream effects. In conclusion, a better understanding of NP-autophagy crosstalk-particularly beyond PS-is crucial to evaluate the real toxic potential of NPs and guide future research in human health and nanotechnology.

Keywords: autophagy; cardiovascular system; gastrointestinal system; mTOR; mitophagy; nanoplastics; nervous system; reproductive system; respiratory system.

Figure 1

Representative illustration of the protein corona and cell damage induced by MPs and NPs. Overview of major cell damage induced by MPs and NPs, and schematic representation of the protein corona, with distinction in the hard and soft corona. Smaller size plays a crucial role in terms of toxicity. MPs: microplastics; NPs: nanoplastics.

Figure 2

Schematic representation of autophagy mechanism. Plastics are durable, low-cost synthetic polymers used widely, but once in the environment, they degrade physically, chemically, and biologically. Factors like UV light, abrasion, microbes, and oxidation break plastics into smaller pieces, eventually forming nanoplastics (NPs). These NPs, due to their tiny size and large surface area, are more reactive and can more easily interact with biological membranes. NPs can cross cellular barriers, be internalized by endocytosis or passive diffusion, and accumulate within cells. This internalization may trigger cellular stress responses, as NPs can carry chemicals, heavy metals, and other pollutant agents on their surface. Moreover, NPs have a more reactive surface, which may generate reactive oxygen species (ROS) and induce oxidative stress, including the activation of the autophagy pathway. Autophagy is a lysosomal-mediated degradation process that primarily degrades damaged cells and dysfunctional organelles to recycle damaged or dysfunctional cellular contents, thereby providing the energy for nascent cells. The initiation of autophagy is regulated by two main sensors: AMPK and mTOR. mTOR and AMPK in the initial steps of the autophagy process through phosphorylation interaction with the ULK1 complex, respectively, whereas AMPK inhibits mTOR activity. AMPK: AMP-activated protein kinase; Atg: autophagy-related gene; LC3: microtubule-associated protein 1A/1B-light chain 3; mTOR: mammalian target of rapamycin; P: phosphate; ROS: reactive oxygen species; ULK1: Unc-51 like autophagy; NPs: nanoplastics; UV: ultraviolet. Created with Bioicons (https://bioicons.com/, accessed on 5 May 2025), licensed under CC BY 4.0.

Figure 3

Overview of the systemic effects of NPs and their impact on autophagy in different organs. NPs can cross biological barriers and accumulate in various tissues, interfering with autophagy and related pathways. In the nervous system, NPs cross the BBB, promoting mitophagy (via AMPK/ULK1 and PINK1/Parkin pathways) and ferroptosis due to iron overload. In the cardiovascular system, NPs inhibit autophagy through lysosomal impairment, decreased LAMP1 expression, and increased ROS. In the respiratory system, they alter mitochondrial function, enhance ferroptosis and ferritinophagy, and reduce MMP. In the gastrointestinal system, NPs disrupt TJs, reduce autophagy and mitophagy, and trigger inflammation and iron dysregulation. Finally, NPs lead to autophagy inhibition in the reproductive system, increased ROS production, and reduced fertility. NPs: nanoplastics; BBB: blood–brain barrier; AMPK: AMP activated protein kinase; ULK1: Unc-51 like autophagy; PINK1: PTEN induced kinase 1; LAMP1: lysosomal-associated membrane protein 1; ROS: reactive oxygen species; MMP: mitochondrial membrane potential; TJs: tight junctions.