Plastics have a prevalent presence in every facet of modern life, from household items to the air, water and soil of the ecosphere1. In recent years, accumulation of plastics and their resistance to physicochemical degradation have raised a great concern to the scientific community and the general public2. Micro- and nano-sized particles are less visible yet plausible derivatives of plastics, and their potential adverse effects on biological systems and the environment have become a topic of scientific and strategic significance in recent years3.
In March 2022, 175 nations signed a historic resolution at the UN Environment Assembly in Nairobi to end plastic pollution and forge an international agreement by the end of 2024. Despite such significant landmark in environmental protection, plastics are here to stay for a foreseeable future, and their environmental and biological impacts will likely linger on much beyond our lifetime.
In 2010, we reported algal photosynthesis inhibition by nanosized polystyrene, one of the earliest studies concerning the ecological footprint of nanoplastics4. This current study5 reported on our new discovery that anionic nanoplastics polystyrene (PS) and poly(methyl methacrylate) (PMMA) could harness the paracellular space of endothelial cells and puncture blood vasculature ex vivo and in vivo, similarly to those observed for inorganic nanoparticles6.
Fig. 1 Vascular endothelial cadherin (VE-cadherin) pairs pop open upon their exposure to anionic nanoplastics.
First, we observed a disruption of the vascular endothelial cadherin (VE-cadherin) junctions to induce transient, micron-sized physical openings in human umbilical vein endothelial cells (HUVECs), elicited by anionic nanoplastics (but not cationic aminated polystyrene) of 20~50 nm in size. Furthermore, PS nanoplastic caused extravasation of Evans Blue Dye in rabbit and swine vessels ex vivo, as well as in the subcutaneous vasculature and multitude organs including the brain, the liver, the spleen, the lungs, the kidneys, and the diaphragms, thereby confirming the prevalent occurrence of endothelial leakiness in vivo to indicate a spread from the vasculature to the whole biological systems by the nanoplastics.
Characteristically, the endothelial leakiness showed both a dose- and time-dependence over cell exposure to both anionic PS and PMMA nanoplastics, mediated by conformational and structural changes to VE-cadherin junctions of endothelial cells engaged with the polymeric nanoparticles but independent of the production of reactive oxygen species, autophagy, and apoptosis of the impacted cells. In addition, we further examined the molecular mechanisms of VE-cadherin dimer rupture by polystyrene and PMMA nanoplastics using discrete molecular dynamics (DMD) and steered DMD simulations, which revealed that the nanoplastics binding reduced the cadherin-dimer stability through an increased inter-domain strain and a reduced entropy.
Fundamentally, nanoplastics-induced vasculature permeability appeared to be biophysical and biochemical in nature resulting from the interactions between the nanoplastics and VE-cadherin junction proteins. This study further revised an earlier belief6 that inorganic nanoparticles, but not polymeric nanoparticles were competent in inducing endothelial leakiness.
Understanding the potential adverse effects of plastics on human health, either via direct exposure or trophic transfer in the ecosphere, is a grand challenge facing the world today. Our current study has uncovered a new route of paracellular transport for nanoplastics, thereby broadening our understanding of the biological effects of plastics, a topic of intense focus and significance as we seek to find new solutions to manage and tame such synthetic materials that are our friend and foe.
- Wang, L., et al. Environmental fate, toxicity and risk management strategies of nanoplastics in the environment: Current status and future perspectives. J. Hazard. Mater. 401, 123415 (2021).
- Prata, J. C. Airborne microplastics: Consequences to human health? Environ. Pollut. 234, 115-126 (2018).
- Liu, Z., et al. Effects of nanoplastics at predicted environmental concentration on daphnia pulex after exposure through multiple generations. Environ. Pollut. 256, 113506 (2020).
- Bhattacharya, P., Lin, S., Turner, J. P., Ke, P. C. Physical adsorption of charged plastic nanoparticles affects algal photosynthesis. J. Phys. Chem. C 114, 16556-16561 (2010).
- Wei, W., et al. Anionic nanoplastic exposure induces endothelial leakiness. Nat. Commun. 13, 4757 (2022).
- Tee, J. K., et al. Nanoparticles’ interactions with vasculature in diseases. Chem. Soc. Rev. 48, 5381–5407 (2019).