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Abstract Ferroptosis is known to mediate the pathogenesis of chemotherapeutic drug‐induced acute kidney injury (AKI); however, leveraging the benefits of ferroptosis‐based treatments for nephroprotection remains challenging. Here, ultrasmall nanodots, denoted as FerroD, comprising the amphiphilic conjugate (tetraphenylethylene‐L‐serine‐deferoxamine, TPE‐lys‐Ser‐DFO (TSD)) and entrapped ferrostatin‐1 are designed. After being internalized through kidney injury molecule‐1‐mediated endocytosis, FerroD can simultaneously remove the overloaded iron ions and eliminate the overproduction of lipid peroxides by the coordination‐disassembly mechanisms, which collectively confer prominent inhibition efficiency of ferroptosis. In cisplatin (CDDP)‐induced AKI mice, FerroD equipped with dual anti‐ferroptotic ability can provide long‐term nephroprotective effects. This study may shed new light on the design and clinical translation of therapeutics targeting ferroptosis for various ferroptosis‐related kidney diseases.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.

Microbubbles as traditional ultrasound contrast agents have seen tremendous developments and bio-applications in the past decades. Due to their outstanding performance, advanced microbubbles as a multifunctional platform combining both imaging and therapy have been increasingly attracting attention. Associated with ultrasound-mediated stimuli, targeting drug transportation with high precision can be established and, as a consequence, a synergistic treatment strategy may prevail, which implies a bright perspective for this brand-new technology. This perspective article will summarize the latest developments on the advanced microbubbles, and review their emerging biomedical applications for the vast community of both applied ultrasound and functional ultrasound-based materials.