Targeting ferroptosis-based cancer therapy using nanomaterials: strategies and applications

Abstract

As an iron-dependent mode of programmed cell death induced by lipid peroxidation, ferroptosis plays an important role in cancer therapy. The metabolic reprogramming in tumor microenvironment allows the possibility of targeting ferroptosis in cancer treatment. Recent studies reveal that nanomaterials targeting ferroptosis have prospects for the development of new cancer treatments. However, the design ideas of nanomaterials targeting ferroptosis sometimes vary. Therefore, in addition to the need for a systematic summary of these ideas, new ideas and insights are needed to make possible the construction of nanomaterials for effectively targeting this cell death pathway. At the same time, further optimization of nanomaterials design is required to make them appropriate for clinical treatment. In this context, we summarize this cross-cutting research area covering from the known mechanism of ferroptosis to providing feasible ideas for nanomaterials design as well as their clinical application. We aim to provide new insights and enlightenment for the next step in developing new nanomaterials for cancer treatment.

Regulatory pathways and drugs associated with ferroptosis in tumors

“…Combining ferroptosis-inducing inducers with bio-nanotechnology for tumor therapy has broad application prospects [ 212 ], but there are still many problems to be solved in clinical ferroptosis-based nanotherapy. First of all, the potential toxic and side effects of nanomaterials should be fully studied to ensure the safety of their application in clinical treatment; in addition, there is an urgent need to develop more precise targeted nanomaterials to ensure tumor-specific triggering of ferroptosis while avoiding off-target toxicity to normal tissues; as nanomaterial-mediated ferroptosis may vary greatly between animals and patients, a more complete assessment system is needed in clinical studies.…”

Assembling p53 Activating Peptide With CeO2 Nanoparticle to Construct a Metallo-Organic Supermolecule Toward the Synergistic Ferroptosis of Tumor

“…Ferroptosis, as a novel tumor therapy strategy, has gained a great lot of attention in tumor development and treatment. As the primary hallmark of cancer is a valid escape from conventional modes of cell death, the traditional cancer therapeutic schedules still face enormous challenges, covering drug resistance, off-target effects, and so on ( Shan et al, 2020 ; Luo et al, 2021a ). Recently, nanoparticles have provided a new form of opportunity for anticancer therapy because of ferroptosis activation.…”

“…However, cancer cells tend to weaken ferroptosis by increasing the expression of antioxidant enzymes ( Li et al, 2022a ) or upregulating prominin2 ( Brown et al, 2021 ) to promote iron transport. Abundant ferroptosis targets and regulatory networks provide an available resource for ferroptosis sensitization ( Luo et al, 2021a ). Among them, p53 as a tumor suppressor can enhance the cell sensitivity to ferroptosis in a direct (transcription-dependent inhibition of SLC7A11 expression) and indirect manner (by regulating amino acid metabolism, iron transport, PUFA metabolism, and antioxidant defense) ( Ji et al, 2022 ).…”

Ferroptosis: A New Road towards Cancer Management

“…The CDGSH iron sulfur domain 2 (CISD2) suppression in HNCCs may increase mitochondrial Fe 2+ and ROS buildup, making cancer more vulnerable to SAS-induced ferroptosis [ 144 ]. To promote ferroptosis, artemisinin and its derivatives may increase the generation of ROS, regulate the Xc − /Gpx4 system axis, and cause ferritin breakdown in the lysosomes [ 145 ]. The activation of ferroptosis by artesunate (ART) kills PDACs and HNCCs [ 146 ].…”