Arsenene Nanodots with Selective Killing Effects and their Low‐Dose Combination with ß‐Elemene for Cancer Therapy

Abstract

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence‐change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell‐cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi‐drug combination strategy with β‐elemene, a plant‐derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on‐demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large‐scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new‐concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

Emerging porous organic polymers for biomedical applications

“…The triggered ROS are highly active and oxidative, which can induce DNA injury and protein damage, leading to cell damage, necrosis, and ultimately death. 252,253 Though PTT and PDT have different mechanisms to kill cancer cells, both of them involve the process to absorb light. Molecules or materials used for PTT or PDT usually have a low band gap in order to efficiently absorb light.…”

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

“…More encouragingly, arsenene, which is a two-dimensional nanomaterial composed of monoelemental arsenic, shows a suitable moderate band structure, high carrier mobility, and good optical properties [ 30 ]. Some recent studies have confirmed that arsenene can be applied not only as an intrinsic transformative valence-activated chemotherapy drug to produce large amounts of reactive oxygen species, but also as a photothermal therapy agent and an in vivo imaging agent, which greatly broadens the biomedical application of arsenical drugs [ 31 , 32 ]. However, the therapeutic compounds inside these liposomes easily leak out before reaching the target site [ 33 ].…”

Recent advances of nanotechnology-based tumor vessel-targeting strategies

“…In addition, inorganic or metal nanomaterials have unique advantages in tumor diagnosis and treatment due to their unique properties, which is also an important development direction in the future. For example, the photothermal effect and anti-angiogenesis of Au NPs, and the anti-tumor effect of arsenene nanodots and surface-oxidized arsenene nanosheets [ 91 , 92 ]. Finally, the development of multifunctional nanocarriers with simple design is also a major challenge of NMs.…”