Copper homeostasis imbalance and cuproptosis: Emerging targets and strategies for gastrointestinal tumor therapy

Table 2 Magnetic resonance imaging-guided copper-based theragnostic strategies

Imaging strategy	Representative platform	Main therapeutic mechanism	Evidence status/limitation	Ref.
MRI-guided copper delivery	Copper-DNA nanoparticles	Tumor imaging, Fenton-like ROS generation, mitochondrial dysfunction, ICD	Shows imaging-therapy integration, but cuproptosis specificity requires further validation	[270]
T1-weighted MRI + PTT/CDT	CuS/Mn2+ hybrid nanogels	MRI-guided photothermal and chemodynamic therapy	Strong imaging signal and synergistic therapy; mainly preclinical	[271]
T1-weighted MRI + PTT	Ultrasmall Cu1.2O nanoparticles	MRI-guided photothermal ablation	Demonstrates copper-based imaging potential; direct cuproptosis markers are limited	[272]
MRI-guided multi-metal therapy	Fe3O4@C/CuOx nanoenzymes	MRI guidance, chemotherapy, PTT, copper/iron-mediated cytotoxicity	Multifunctional but mechanistically complex	[273]
TME-responsive MRI	Cu-Fe peroxide-containing nanoparticles	Cu-assisted iron cycling and Fenton amplification	Strong redox rationale; biosafety and clearance need validation	[274]
MRI-guided PDAC therapy	Collagenase-modified copper-containing hollow mesoporous silica nanoparticles	Stromal modulation and copper-induced cytotoxicity	Tumor-specific design for PDAC; translation remains early	[255]
MRI-guided ferroptosis/cuproptosis/CDT	CuO2-loaded dendritic macromolecule/metal-polysaccharide nanocomposites	TME regulation, ROS amplification, ferroptosis and cuproptosis	Promising combination design, but pathway attribution remains challenging	[275]
MRI + NIR-triggered cascade therapy	Cu/Mn-doped iron oxide nanocrystals	Drug release, Cu2+ chelation, ferroptosis/cuproptosis cascade	Integrates imaging and cascade therapy; preclinical validation needed	[276]
Activatable MRI + PDT/CDT	GSH/H2O2-responsive magnetic Cu2+ nanocomplex	“On-off” MRI activation, Cu+ release, hydroxyl radical generation, PDT enhancement	Smart activation design; in vivo specificity requires further testing	[277]
MRI-guided chemo-immunotherapy	Phosphorus dendrimer-copper complexes	Mitochondrial dysfunction, ER stress, immunotherapy enhancement	Illustrates theragnostic potential, but not exclusively cuproptosis-driven	[278]

MRI: Magnetic resonance imaging; ROS: Reactive oxygen species; ICD: Immunogenic cell death; PTT: Photothermal therapy; CDT: Chemodynamic therapy; PDAC: Pancreatic ductal adenocarcinoma; TME: Tumor microenvironment; NIR: Near-infrared; GSH: Glutathione; ER: Endoplasmic reticulum.