Abstract
Accumulated studies indicate that zero-valent iron (ZVI) nanoparticles demonstrate endogenous cancer-selective cytotoxicity, without any external electric field, lights, or energy, while sparing healthy non-cancerous cells in vitro and in vivo. The anti-cancer activity of ZVI-based nanoparticles was anti-proportional to the oxidative status of the materials, which indicates that the elemental iron is crucial for the observed cancer selectivity. In this thematic article, distinctive endogenous anti-cancer mechanisms of ZVI-related nanomaterials at the cellular and molecular levels are reviewed, including the related gene modulating profile in vitro and in vivo. From a material science perspective, the underlying mechanisms are also analyzed. In summary, ZVI-based nanomaterials demonstrated prominent potential in precision medicine to modulate both programmed cell death of cancer cells, as well as the tumor microenvironment. We believe that this will inspire advanced anti-cancer therapy in the future.
Highlights
According to GLOBOCAN 2020, cancer is one of the leading chronic diseases causing death before the age of 70 years in many countries [1]
Accumulated evidence showed that zero-valent iron (ZVI) NPs generated significantly higher Reactive oxygen species (ROS) in cancerous cells, loss of mitochondria membrane potential associated with distinct lysosomal activity and intracellular abundance, altered mitochondria structure, and energy metabolism
Yang demonstrated that aged ZVI NPs had increased oxygen composition and reduced cytotoxicity, as well as attenuated ROS. These findings suggested that the maintenance of the non-oxidized ZVI components is important for their cancer-killing ability
Summary
According to GLOBOCAN 2020, cancer is one of the leading chronic diseases causing death before the age of 70 years in many countries [1]. Pharmacokinetics and pharmacodynamics are critical to accumulate sufficient therapeutic doses in cancer lesions while minimizing their retention in major organs Nanomaterials, such as VYXEOS® or BIND-014® , were designed to carry anti-cancer compounds alone or with active targeting to achieve targeted drug delivery [14,15,16]. In 2008, that nanoparticles (NPs) that possess the strong endogenous anti-cancer activity and selectively suppress cancer cells were reported [23]. Despite metal oxide nanoparticles being widely used in therapeutic applications (e.g., zinc, iron, titanium, copper, etc.), zerovalent iron (ZVI) NPs exhibited distinct anti-cancer properties to modulate solid tumors in comprehensive approaches. Accumulated evidence showed that ZVI NPs generated significantly higher ROS in cancerous cells, loss of mitochondria membrane potential associated with distinct lysosomal activity and intracellular abundance, altered mitochondria structure, and energy metabolism. The underlying mechanisms will be addressed, from the molecular to the systemic level
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