Black Phosphorus Quantum Dots Cause Nephrotoxicity in Organoids, Mice, and Human Cells

Abstract

Quantum dots (QDs) have numerous potential applications in lighting, engineering, and biomedicine. QDs are mainly excreted through the kidney due to their ultrasmall sizes; thus, the kidneys are target organs of QD toxicity. Here, an organoid screening platform is established and used to study the nephrotoxicity of QDs. Organoids are templated from monodisperse microfluidic Matrigel droplets and found to be homogeneous in both tissue structure and functional recapitulation within a population and suitable for the quantitative screening of toxic doses. Kidney organoids are proved displaying higher sensitivity than 2D‐cultured cell lines. Similar to metal‐containing QDs, black phosphorus (BP)‐QDs are found to have moderate toxicity in the kidney organoids. The nephrotoxicity of BP‐QDs are validated in both mice and human renal tubular epithelial cells. BP‐QDs are also found to cause insulin insensitivity and endoplasmic reticulum (ER) stress in the kidney. Furthermore, ER stress‐related IRE1α signaling is shown to mediate renal toxicity and insulin insensitivity caused by BP‐QDs. In summary, this work demonstrates the use of constructed kidney organoids as 3D high‐throughput screening tools to assess nanosafety and further illuminates the effects and molecular mechanisms of BP‐QD nephrotoxicity. The findings will hopefully enable improvement of the safety of BP‐QD applications.

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment

“…Characterization of these QDs was reported in our previous study, including the morphology, size, hydrodynamic size, and zeta potential. [ 6 ] Then, we examined the cell viability of these QDs in human lung adenocarcinoma epithelial A549 cells. The A549 cells are a typical model of the lung epithelium.…”

“…However, the safety of engineered nanomaterials (ENMs) in regards to human health and ecoenvironmental sustainability has been questioned by researchers and the public. [ 1,2 ] There are many studies show that ENMs might cause adverse effects to human or animals, such as developmental defect, [ 3 ] reproductive abnormality, [ 4 ] organ dysfunction, [ 5,6 ] and even promoting tumorigenesis. [ 7 ] Although numerous studies have been conducted for nanosafety evaluation using in silico, in vitro, and in vivo methods, a widely accepted assessment framework for ENMs remains to be built.…”

Nanoparticle-Induced m6A RNA Modification: Detection Methods, Mechanisms and Applications

“…Recently, we established a 3D high-throughput screening system using constructed kidney organoids to study the nephrotoxicity of black phosphorus quantum dots (BPQDs) [ 104 ]. Interestingly, we found significant endoplasmic reticulum (ER) stress and insulin sensitivity induced by BPQDs in the kidney.…”

Bioengineering applications of black phosphorus and their toxicity assessment

“…48 Recently, NBP was found to cause nephrotoxicity in mice. He et al 133 revealed that bare NBP with a hydrodynamic size of 15.1 ± 1.8 nm induced a significant toxic effect on the kidney of BALB/c mice after being intragastrically administered with 1 mg kg −1 bw −1 d −1 NBP for 7 days. After the treatment, the uric acid (UA) content and creatinine content in the serum of mice were significantly increased and decreased, respectively (Fig.…”