Table 1.

Antitumor effects of rhodium complexes and their mechanism of action.

Complex	Oxidation state	Mechanism of action	Targets	Cancer cells/animal models	Ref.
[RhCl(IBuMe)(COD)] (1)	+1	Prevented DNA replication, altered cell migration, and induced DNA condensation	DNA	HCT116	[20]
[Rh(η5C5Me5)(pta)Cl2] (2) [Rh(η5C5Me5)(pta)2Cl]Cl [Rh(η5C5Me5)(CO)(pta)]	+1	Interacted with DNA or protein	DNA, protein	HT29, A549, T47D	[21]
RhCl(NHC)(COD) (3)	+1	Inhibited TrxR activity and induced apoptosis	TrxR, DNA, albumin	HT-29, U-87, Ishikawa, MCF-7	[23,24]
Rh(I)(NHC)(COD)X (X is Cl or I) (4)	+1	Induced DNA damage and affected cell metabolism	MAPK signaling	HT-29, MDA-MB-231	[25]
Rh(I)-NHC complexes containing 4,5-diarylimidazoles (5)	+1	Inhibited the expression of the TrxR system, promoted intracellular ROS accumulation, damaged mitochondrial membrane potential, promoted cancer cell apoptosis, and blocked the cells in the G1 phase	TrxR	HepG2, HT-29, MCF-7/HCC nude mouse	[26]
Rh(I)-NHC complexes containing 4-ethylthio-1,8-naphthalimides (6)	+1	Inserted the planar bases of B-DNA via an intercalation mechanism and stacking on top of the quartets of G-quadruplex structures	DNA	MCF-7, HT-29	[29]
Rh(I)(COD)(NHC)I complexes containing 1,8-naphthalimide-based emitting ligands (7)	+1	Localization to the endoplasmic reticulum led to apoptosis	endoplasmic reticulum	HT-29, PT-45	[30]
[Rh2(bridge)4] (8) (bridge = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate)	+2	Stored in HAS and then transferred to the tumor cell by passive diffusion	HSA	Ehrlich tumor-bearing mice	[36]
[Rh2(OAc)3(bpy)(H2O)2]PF6 (9)	+2	Interacted with DNA	DNA	Caco-2	[37]
Rh(II) complex containing 2-benzoylpyridine (10)	+2	Increased expression of caspase-3 and PARP via the mitochondrial and the death receptor pathways, induced G1 cell cycle arrest and apoptosis	Bcl-2 family proteins	HepG2	[38]
C188-9-Rh2 (11)	+2	Targeted the CCD and blocked the STAT3 function	STAT3	HL-60, Kasumi-1, MOLM-13	[39]
Rh(II) carboxy-fluorophore conjugates (12)	+2	Inhibited STAT3 phosphorylation	STAT3	NIH 3T3, MOLM-13	[40]
Rh2(II, II) complexes containing bidentate or tridentate polypyridine (13)	+2	Released immune suppression and activated antitumor T cell	TAMs	TAMs, MDA-MB-231	[42]
RhCl2(Hpz)4][RhCl4(Hpz)2, RhCl3(tpy), [RhCl3(tpta)]ꞏH2O, [Rh(tpy)2(Him)]Cl3ꞏ3H2O (14)	+3	The interaction with DNA, via the formation of coordination N-Rh bond with guanine or cytosine bases, restricted the DNA migration	DNA	HCV29T	[44]
[cis-Rh(dppz)(phen)]Cl2+ (15)	+3	Interacted with DNA through covalent binding and nicking	DNA	GN4, M109, KB	[45]
[Rh(L)(chrysi)(PPO)]2+ (16)	+3	Bound specifically to DNA base pair mismatches and killed MMR-deficient cells	DNA	HCT116	[49]
[Rh(chrysi)(phen)(PPO)]2+ (17)	+3	Induced DNA damage response, arrested cell cycle, and inhibited DNA replication and transcription	DNA	HCT116	[50]
[Rh(chrysi)(phen)(PPO)] Cl2 (18)	+3	Activated the DNA damage response, and inhibited DNA replication and cell proliferation, leading to cell death by necrosis	DNA	HCT116 xenograft tumor model	[52]
rac-[Rh(ppy)2(C≡(N-L)2]+, rac-[Rh(bzq)2(C≡(N-L)2]+ (19)	+3	Inhibited JAK2 phosphorylation	JAK2	HEL	[52]
Rh(III) complexes containing 4-(pyridin-2-yl)benzaldehyde (20)	+3	Targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization	STAT3	A357, A2058/melanoma tumor-bearing mice	[53]
[Rh(bzimpy)Cl3] (21)	+3	Interacted with DNA through groove binding mode, bound to BSA through the formation of hydrogen bonds and van der Waals forces	DNA, BSA	K562 HT-29 MCF-7	[54]
Rh(III) complex containing 4-chloro-2-phenylquinoline C^N (22)	+3	Disrupted the interaction of LSD1-H3K4me2 and enhanced the amplification of p21, FOXA2, and BMP2 gene promoters	LSD1	PC3, 22RV1	[55]
Rh(III) complex containing two 2-phenylquinoline C^N ligands and a 4,4′-diphenyl-2,2′-bipyridine N^N ligand (23)	+3	Induced accumulation of H3K4me3 and H3K4me2 level, arrested cell cycle at G1 phase, targeted of KDM5A, and henced upregulating p27	KDM5A	MDA-MB-231, 4T1/4T1 tumor-bearing mouse	[56]
[Rh2(C∧N)4Cl2]PF6 (where C∧N=7-chloro-2-phenylquinoline) (24)	+3	Reduced phosphorylation of CDC2 at Y15, increased DNA damage, and resulted in blocked mitosis	Wee1	MDA-MB-231	[57]
SAHA-derived [Rh(Cp∗)Cl2]2 (25)	+3	Inhibited HDAC6 activity and demonstrated anti-angiogenic activity by down-regulating VEGFR2	HDAC6	HCT116, NCI-H460, SiHa, SW480	[58]
Rh(III) phthalocyanine complexes (26)	+3	The cooperative action of the photouncaging reaction and the photochemical generation of reactive oxygen species was indicated to induce cell deaths		Hela	[60]
Rh(III) 2-Benzoylpyridine Thiosemicarbazone Complexes (27)	+3	Reprogramming the immune and metabolic tumor microenvironments through induction of ICD and inhibition of dual-energy metabolism	mitochondria	A549, ADR/Aggressive A549/ADR pulmonary lung metastasis models	[61]
Rh(III) complexes containing 4-methyl-2-N-(2-pyridylmethyl)-aminophenol ligands (28)	+3	Activates T-lymphocyte infiltration into the tumour site by down-regulating the Wnt/β-catenin signaling pathway, thereby triggering an antitumor immune response	Wnt/β-catenin	4T1, MDA-MB-231/4T1 tumor-bearing mouse	[62]
[Rh(ppy)2(dppn)]PF6 (29)	+3	Specifically bind to mtDNA to cause the cytoplasmic release of mtDNA fragments to activate the cGAS-STING pathway	mtDNA	HeLa, U14 tumor-bearing mouse	[63]