Table 1.

Antitumor effects of ferroptosis inducers (concomitant immunotherapy)

Authors	Drugs	Tumor types	Therapeutic mechanisms	References
Ding Q, et al.	BQR@MLipo	Bladder cancer	Inhibits of DHODH activity, induces lipid peroxidation and ferroptosis in tumor cells. Release of DAMPs induces the cGAS-STING pathway to enhance DC cells maturation.	[40]
Zhang L, et al.	COF-919	TNBC	Promotes the production of ROS, induces lipid peroxidation and ferroptosis. Enhances the infiltration capacity of CD8+T cells to remodel TME.	[43]
Guo S, et al.	FeGd-HN@TA-Fe2+-SN38 nanoparticles	TNBC	Induces ferroptosis in tumor cells. The release of IFN-β and IFN-γ stimulates the activation of NK cells and CD8+T cells.	[46]
Wang WJ, et al.	FerroceneAppended Iridium(III) Diphosphine Complex	TNBC	Induces of lipid peroxidation and ferroptosis in tumor cells, promotes the release of DAMPs and enhances immunogenic cell death in tumor.	[51]
Wang Z, et al.	Cu/ZIF-8@U-104@siNFS1-HA	Osteosarcoma	Inhibits GSH and GPX4 expression, promotes tumor ferroptosis. Increases M1-type macrophage polarisation, induces antigen-presenting cells maturation, inhibits Treg cells function and promotes tumor infiltration of CD8+T cells.	[48]
Han W, et al.	ZnP@DHA/Pyro-Fe core-shell nanoparticles	Colon cancer	Induces ROS generation and ferroptosis in tumor cells. Release of DAMPs induce DC cells maturation and enhance tumor infiltration of CD8+T cells.	[52]
Li LG, et al.	DHA@MIL-101	Lung cancer	Induces ROS accumulation, lipid peroxidation and ferroptosis in tumor cells. Release of DAMPs activate NF-κB through the cGAS/STING pathway and induces M1-type repolarisation of TAM, which also stimulate DC cells maturation.	[53]
Han N, et al.	Dihydroartemisinin	Lung cancer	Inhibits of GPX4 expression, induces lipid peroxidation and ferroptosis. Subsequent endoplasmic reticulum stress and damaged DNA fragments improve anti-tumor immune responses.	[54]
Liang JL, et al.	HBMn-FA	TNBC	Induces of oxidative stress and ferroptosis in tumor cells, and release of DAMPs activate the cGAS-STING pathway to further promote DC cells maturation.	[55]
Zhang Q, et al.	TCPP-TK-PEGPAMAM-FA	TNBC	Inhibits the HIF-1α pathway, enhances lipid peroxidation and ferroptosis. Released DAMPs and antigens stimulate anti-tumor immune responses.	[47]
Zhou Y, et al.	PAMAM	TNBC	Blocks GPX4 and FSP1 expression and induces lipid peroxidation and ferroptosis. Released DAMPs enhances DC cells maturation and infiltration of CD8+T cells into the TME.	[44]
Liu Z, et al.	MTX-LDH@MnO2 nanoplatform	TNBC	Inhibits BH4 biosynthesis, depletes GSH and GPX4 and promotes ferroptosis. Release of DAMPs further induce anti- tumor immune responses.	[45]
Xie B, et al.	FeAMV	TNBC	Inhibits the function of the xCT system, GSH and GPX4, induces ROS accumulation and promotes ferroptosis. Antigens and DAMPs released after ferroptosis can promote anti- tumor immune responses.	[56]
Song WF, et al.	Self-assembled copper-alanine nanoparticles	TNBC	Induces the Fenton reaction and depletes GSH, promotes a massive build-up of ROS and induces ferroptosis. ROS also activates the anti- tumor immune response.	[57]
Yu Y, et al.	MFE-NCPs	Colon cancer	Inhibits of BH4 biosynthesis, promotes oxidative stress and ferroptosis. DAMPs released by ferroptosis in tumor cells enhance anti- tumor immune responses.	[58]
Li K, et al.	Cu2 − xSe/ZIF-8@Era-PEG-FA	TNBC	Inhibits GPX4 and GSH expression, induces ferroptosis. Reduction of miR301 in tumor cell exosomes promotes M1-type repolarisation of TAM. Activation of CD8+T cells and secretion of IFN-γ induce ferroptosis in tumor cells.	[59]
Wang S, et al.	TPL@TFBF	Melanoma	Promotes intracellular ROS production in tumor cells and induces lipid peroxidation and ferroptosis through Fenton reaction and inhibition of NRF2-related pathways. Released DAMPs induce anti-tumor immune responses.	[49]
Liu P, et al.	Metal-phenolic networks nanoplatform	Melanoma	Increases lipid peroxidation and ferroptosis in tumor cells, released DAMPs promote anti- tumor immune responses. T-cell-derived IFN-γ hinders the function of the xCT system in tumor cells. MPNs also blocks PD-L1 protein expression in tumor cells.	[50]
Xie L, et al.	PFG-MPNs	Melanoma	Induces Fenton reaction, lipid peroxidation and ferroptosis in tumor cells, release of DAMPs promote DC cells activation. T-cell-derived IFN-γ hinders xCT system function as well as GSH and GPX4 expression in tumor cells.	[60]
Lei L, et al.	ZN-FU MNS	Colon cancer	Damages mitochondria and produces ROS, induces lipid peroxidation and ferroptosis. Release of DAMPs activate DC cells and promote anti-tumor immune responses.	[61]
Pei Z, et al.	VS2-PEG	Colon cancer	Depletes intracellular GSH and GPX4, induces ferroptosis of tumor cells, promotes IL-1β efflux, inhibits pro-tumor immune cells function, promotes repolarisation M1-type macrophages.	[62]
Ruan Y, et al.	E. coli@Cu2O microbial nanohybrid	Colon cancer	Reduces GSH and GPX4 activity, induces lipid peroxidation and ferroptosis. Release of DAMPs promote anti-tumor immune response.	[63]
Deng X, et al.	Ca & Mn dualion hybrid nanostimulator	TNBC	Reduces GSH and GPX4 activity, induces lipid peroxidation and ferroptosis. Release of antigen activates STING signalling activation, promotes M1-type polarisation of TAM and DC cells maturation.	[64]
Wang H, et al.	PEGylated Manganese–Zinc Ferrite Nanocrystals	Prostate cancer	Inhibits GSH and GPX4 activity and promotes ferroptosis. Release of IFN-γ and antigen synergistically promote anti-tumor immune responses.	[65]
Li Q, et al.	Fe3O4-DHJS@HRM nanoparticles	Osteosarcoma	Promotes Fenton reaction, inhibits NRF2 pathway-related antioxidant functions, and induces lipid peroxidation and ferroptosis. Release of DAMPs induces anti-tumor immune responses, induces M1-type polarisation of TAM.	[66]
Chen M, et al.	D@FMN-M	TNBC	Depletes GSH and GPX4 expression, triggers Fenton reaction and releases ROS, induces ferroptosis in tumor cells. Release of tumor cell-associated antigens induce activation of anti-tumor immune responses.	[67]
Liu B, et al.	Fe3O4-siPD-L1@M− BV2	Glioblastoma	Induces ferroptosis and reduces PD-L1 expression in tumor cells and releases tumor-associated antigens that induce anti-tumor immune responses.	[68]
Yang N, et al.	CFA/PRV@MM	TNBC	Depletes GSH and GPX4 expression, inhibits the antioxidant capacity of FSP1/CoQ10 and induces lipid peroxidation and ferroptosis in tumor cells. Released DAMPs induce DC cells maturation and M1-type macrophage polarisation.	[69]
Yang Q, et al.	CP nanoformulation	Melanoma	Promotes ferroptosis, blocks PD-L1 expression by inhibiting the NF-κB pathway and p38/MAPK pathway, and enhances anti-tumor immune responses.	[70]
Liu J, et al.	IFNγ/uMn-LDHs	TNBC	Depletes GSH and GPX4 expression, inhibits the function of the xCT system and promotes ferroptosis in tumor cells. Release of DAMPs induce an anti-tumor immune response.	[71]