TABLE 1.

Introduction of the more innovative methods and their respective advantages and disadvantages.

Approaches	Characteristics	Advantages	Disadvantages
Aniline-derived Probe	Lipid-derived electrophiles (LDEs) produced by Ferroptosis can influence the protein function in the manner of covalently modifying the protein. Aniline-derived probe can detect protein carbonylations and novel cysteine sites in the process of cell ferroptosis.	1. This is a commercial compound that is cheap and easy to obtain	—
		2. Compared with classic hydrazine and hydroxylamine probes, it has higher sensitivity and is very suitable for studying endogenous carbonylation modifications with weak signals
		3. The chemical properties of the adduct of the aniline probe and the peptide are very stable, which can avoid fragmentation during sample preparation and computer application.
Arginine-rich manganese silicate nanobubbles (AMSNs)	AMSNs is a novel tumor targeted nanoparticle that inhibits the growth of cancer cells by effectively consuming glutathione and synergistic chemotherapy drugs. During this process, the ferroptosis pathway is activated.	1. The particle size of nanobubbles is about 6.2 nm, and the potential is -17.6mv. It has a high specific surface area, porosity, colloidal stability, long half-life (4.07 h) and tumor targeting recognition function. Its lethal effect is significantly lower than that of cancer cells	1. There is still a challenge to kill cancer by consuming GSH because of the low consumption rate of GSH.
		2. AMSNs have better degradability than solid nanomaterials (such as MnO). In the process of consuming GSH, the color of AMSNs solution gradually becomes lighter, while the color of solid nanomaterials changes less, indicating that manganese ions in AMSNs are released faster and more easily degraded	—
		3. AMSNs, as a contrast agent for NMR, are easily degraded in the microenvironment of tumor cells (weak acid and high GSH concentration) and produce Mn (II) to help enhance the contrast effect of NMR T1-weighted imaging. AMSNs can be used as anti-cancer drug carriers or anti-cancer agents, effectively inhibiting the growth of cancer cells	—
Covalent inhibitor that selectively targets GPX4	The author synthesized a series of GPX4 covalent inhibitors containing electrophilic warhead and nitrile oxidation to selectively inhibit GPX4 activity and induce ferroptosis in drug-resistant tumor cells. This is a novel highly selective probe molecule for GPX4-mediated detection, providing a strategy for broadening the selection of covalent inhibitor warheads.	1. Compared with the previous covalent inhibitor-containing chloroacetamide, it has significantly superior pharmacokinetic properties	1. JKE-1674, the intermediate of ML-210, will decompose when stored in DMSO for a long time.
		2. It can more specifically induce cell ferroptosis through GPX4, and the signal pathway is single and clear. It is more suitable as a probe to study related pathways	—
Dual-function fluorescent probe (H-V)	The H-V probe can be used to detect the cytoplasmic Viscosity and OH changes during ferroptosis with a typical molecular rotor structure. With the increase of microenvironmental viscosity, the fluorescence of the probe was enhanced.	1. The unique hydroxylation of OH on aromatic compounds results in high selectivity
		2. A strong electron-donating methoxy group is added to enhance the H-V probe’s capture ability of OH, thereby improving the detection sensitivity
		3. The probe can work more effectively in the cytoplasm. The probe can detect viscosity and OH in two independent channels
		4. It has good biocompatibility
SRF@FeIIITA nanoparticles	SRF@FeIIITA nanoparticles are formed by the self-assembly of iron ions (Fe3+) and tannic acid (TA) on the surface of sorafenib nanocrystals. SRF inhibits GPX4 to induce ferroptosis. The Fe2+ sustainably reduced from TA was toxic to cancer cells. The photosensitizers assist in photodynamic therapy in conjunction with ferroptosis.	1. The prepared nanomedicine selectively causes ferroptosis of tumor cells, which is low cytotoxicity	—
		2. Many functional substances can adhere to the surface of polyphenols to facilitate the expansion of deep applications based on ferroptosis treatment methods
Hypoxia-responsive micelles	Hypoxia-responsive micelles, acting as ferroptosis inducers, promote ferroptosis against solid tumors by reducing glutathione and thioredoxin in hypoxia.	1. Compared with other chemotherapeutic drugs (including procaspase-3 agonist, PAC-1, 1541B, nucleoside analog gemitabine, 5-F, etc.), the median lifetimewas found to be short	—
		2. The same dose of these compounds showed better than RSL3 and Erastin in inhibiting the proliferation of HCT116 and A549 cancer cells
		3. These compounds exert their ability to inhibit tumor proliferation by inducing ferroptosis in tumor cells.
		4. Novel structure and excellent activity.