Surface-Charge-Driven Ferroptosis and Mitochondrial Dysfunction Is Involved in Toxicity Diversity in the Marine Bivalve Exposed to Nanoplastics

Abstract

Nanoplastics (NPs) pervade daily life, posing serious threats to marine ecosystems. Despite the crucial role that surface charge plays in NP effects, there is a substantial gap in our understanding of how surface charge influences NP toxicity. Herein, by exposing Ruditapes philippinarum (R. philippinarum) to both positively charged NPs (p-NPs) and negatively charged NPs (n-NPs) at environmentally relevant particle number levels for a duration of 35 days, we unequivocally demonstrate that both types of NPs had discernible impacts on the clams depending on their surface charge. Through transcriptomic and proteomic analyses, we unveiled the primary mechanisms behind p-NP toxicity, which stem from induced mitochondrial dysfunction and ferroptosis. In contrast, n-NPs predominantly stimulated innate immune responses, influencing salivary secretion and modulating the complement and coagulation cascades. Furthermore, in vitro tests on clam immune cells confirmed that internalized p-NPs triggered alterations in mitochondrial morphology, a decrease in membrane potential, and the initiation of ferroptosis. Conversely, n-NPs, to a certain extent, moderated the expression of genes related to immune responses, thus mitigating their adverse effects. Taken together, these findings indicate that the differential surface-charge-driven ferroptosis and mitochondrial dysfunction in clams play a critical role in the toxicity profile of NPs, providing an insightful reference for assessing the ecological toxicity associated with NPs.

Biodegradable Bismuth Nanostructures as a Ferroptosis Inducer for Phototherapy of Breast Cancer

“…It maintains membrane lipid bilayer homeostasis, allowing tumor cells to evade ferroptosis. Inducing ferroptosis requires ROS accumulation and inducers that can deactivate GSH. , Consequently, reducing intratumor GSH to cause ferroptosis is a practical approach to enhancing PDT. Various methods, including heavy metal ions and semiconductor holes, can deplete GSH in tumor cells. , …”