ROS-Mediated Selective Killing Effect of Black Phosphorus: Mechanistic Understanding and Its Guidance for Safe Biomedical Applications

Abstract

Black phosphorus (BP)-based nanomaterials have distinguished advantages and potential applications in various biomedical fields. However, their biological effects in physiological systems remain largely unexplored. Here, we systematically revealed a reactive oxygen species (ROS)-mediated mechanism for the selective killing of cancer cells by BP-based nanosheets. The treatment with BP-based materials can induce higher levels of ROS in cancer cells than in normal cells, leading to significant changes in the cytoskeleton, cell cycle arrest, DNA damage, and apoptosis in tumor cell lines. We revealed that the decreased superoxide dismutase activity by lipid peroxides could be an essential mechanism of the selectively higher ROS generation induced by BP-based nanosheets in cancer cells. In addition, the selective killing effect only occurred within a certain dosage range (named “SK range” in this study). Once exceeding the SK range, BP-based materials could also induce a high ROS production in normal tissues, leading to detectable DNA damage and pathological characteristics in normal organs and raising safety concerns. These findings not only shed light on a new mechanism for the selective killing of cancer cells by BP-based materials but also provide deep insights into the safe use of BP-based therapies.

Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy

“…evaluated. The acute degradation of BPNS in cancer cells can yield high levels of phosphate anions and immediately lead to the death of cancer cells 48,62 . We conceived that the therapeutic effects of BPNS could be precisely controlled by the addition of Cu 2+ ions and NIR irradiation, as they co-modulate the degradation of BPNS.…”

Recent advances of two-dimensional materials in smart drug delivery nano-systems

“…Due to sensitive response to external stimuli, 2D materials are more controllable compared to traditional drug delivery platform (such as polymers). 2D materials have a huge specific surface area, resulting in an effective load of fluorescent dyes, targeting molecules and therapeutic drugs [ [192] , [193] , [194] , [195] ]. In addition, many 2D materials exhibit great phototherapy performance, which makes combined therapy possible [ [196] , [197] , [198] , [199] ].…”

Biomedical Application of Reactive Oxygen Species–Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases

“…Reactive oxygen species–responsive materials refers to materials capable of responding to those elevated ROS, such as H 2 O 2 , O 2·− , 1 O 2 , and so on. There have been great progress in nanomedicines and responsive materials used in biomedical fields (Tao et al, 2017 , 2019 ; Qiu et al, 2018 , 2019 ; Luo et al, 2019 ; Feng et al, 2020 ; Hu et al, 2020 ; Kong et al, 2020 ; Tang et al, 2020 ; Xie et al, 2020 ). ROS-responsive nanocarriers have some unique advantages for therapy compared with these reported materials.…”