Black Phosphorus Quantum Dot Induced Oxidative Stress and Toxicity in Living Cells and Mice

Abstract

Black phosphorus (BP), as an emerging successor to layered two-dimensional materials, has attracted extensive interest in cancer therapy. Toxicological studies on BP are of great importance for potential biomedical applications, yet not systemically explored. Herein, toxicity and oxidative stress of BP quantum dots (BPQDs) at cellular, tissue, and whole-body levels are evaluated by performing the systemic in vivo and in vitro experiments. In vitro investigations show that BPQDs at high concentration (200 μg/mL) exhibit significant apoptotic effects on HeLa cells. In vivo investigations indicate that oxidative stress, including lipid peroxidation, reduction of catalase activity, DNA breaks, and bone marrow nucleated cells (BMNC) damage, can be induced by BPQDs transiently but recovered gradually to healthy levels. No apparent pathological damages are observed in all organs, especially in the spleen and kidneys, during the 30-day period. This work clearly shows that BPQDs can cause acute toxicities by oxidative stress responses, but the inflammatory reactions can be recovered gradually with time for up to 30 days. Thus, BPQDs do not give rise to long-term appreciable toxicological responses.

Black phosphorus as a versatile nanoplatform: From unique properties to biomedical applications

“…Mechanisms responsible for induced in vitro cytotoxicity of BP might include (1) formation of intracellular reactive oxygen species (ROS) and 2complete or partial disintegration of cell membranes upon their interaction with BP. 126,127 Thus, for biomedical applications, size and concentration of BP are also needed to be optimized.…”

Black phosphorus: A novel nanoplatform with potential in the field of bio-photonic nanomedicine

“…The results of this paper indicate that FLBP is appropriate for biomedical applications. Mu et al 149 explored toxicological studies on BP quantum dots (BPQDs), which underwent faster renal¯ltration than BP nanosheets, systemically with cell and animal model. Comparing the cells viability and the endocellular ROS levels in experimental group with different concentrations of BPQDs and the control group, they found that the cytotoxicity of BPQDs is mainly derived from ROS produced by itself.…”

Review of toxicological effect of quantum dots on the liver

“…Similar studies showed that black phosphorus QDs were mainly accumulated in the liver and spleen after intraperitoneal injection and caused a small amount of hepatocyte apoptosis on the first day after exposure, but apoptotic cells are almost absent after 7 and 30 days, suggesting that black phosphorus QDs have no long‐term toxicity. It is emphasized that no apparent damages was detected in all organs, particularly in the liver and spleen during the entire time (Mu et al, ). This significant difference between in vivo and in vitro studies was mainly due to the complexity of the environment in the body.…”

“…Tang et al, 2016;Tang et al, 2017 Black phosphorus QDs: 2.7 nm Male C57BL/ 6mice Peritoneal cavity 0.34 mg per mouse, observed 1, 7 and 30 days QDs caused oxidative stress in the liver after 1 day of exposure to QDs and returned to normal after 7 days;QDs caused a small amount of hepatocyte apoptosis after 1 day, and apoptotic cells were almost absent at 7 and 30 days as well as did not cause significant liver function impairment and pathological injury. Mu et al, 2017 ALT, alanine aminotransferase; AST, aspartate aminotransferase; GQDs, graphene quantum dots; QD-MEA, 2-aminoethanethiol-coated quantum dots; mtROS, mitochondrial reactive oxygen species; QD-MPA, mercaptopropionic acid-coated quantum dots; QD-PEG, polyethylene glycol-coated quantum dots; QDs, quantum dots.…”