Table 1.

Overview of the different magnetic nanostructure-based combinatorial immunotherapy approaches.

Magnetic Nanostructure	Surface Chemistry	Immunotherapeutic Drug	Therapeutic Approach	Remarks	Ref.
Iron nanoparticles (nano-aAPC)	Dextran functionalized with both MHC-Ig dimer and anti-CD28 antibody	MHC-Ig dimer, anti-CD28 antibody	Adoptive immunotherapy	Application of an external magnetic field induced nano-aAPC aggregation on naive cells, enhancing T cell proliferation in vitro and following adoptive transfer in vivo.	[60]
Iron oxide nanoclusters (Magnetosome)	Cancer cell-derived plasma membrane functionalized with anti-CD205 antibody	TAAs, CpG ODN	Vaccine/Immune adjuvant	Cancer cell membranes serve as a reservoir of TAAs and their co-delivery with TLR9-agonist lead to a great proliferation of T-cells with superior cytotoxic activity. The application of an external magnet enhanced lymph node retention and anti-CD205-mediated CD8+ DCs targeting of nanoparticles.	[59]
Iron oxide nanoclusters (IO-LPMONs)	Mesoporous organosilica shell having large pore size	OVA antigen	Vaccine/TAMs repolarization	Simultaneous T cell activation and TAMs repolarization induced strong inhibition of tumour growth.	[138]
Iron oxide nanospheres (IO@FuDex3)	Fucoidan and dextran functionalized with multiple antibodies	Anti-PD-L1, anti-CD3 and anti-CD28 antibodies	T cell activation/Immune checkpoint inhibitor	IO@FuDex3 can directly induce T-cell activation and block the immunosuppressive PD-L1 pathways via intravenous administration. The combination of IO@FuDex3 and magnetic navigation demonstrated a highly improved therapeutic efficacy.	[116]
Iron oxide nanoparticle-loaded micelles (poly(I:C)–Pt(IV)–IONP micelles)	DSPE-PEG(2000)-Pt(IV) prodrug functionalized with poly(I:C)	Poly(I:C)	Immune adjuvant/Chemotherapy	Pt(IV) prodrug synergized with TLR3-agonist inducing a more potent activation of DCs than cisplatin and poly(I:C).	[139]
Iron oxide superparticles (Fe3O4-R837 SPs)	Poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) copolymer	R837, anti-PD-L1 antibody	ICD/Immune adjuvant/Immune checkpoint inhibitor	Photothermal therapy promotes cancer cells killing, with consequent release of TAAs, and triggers the release of R837 immune adjuvant for a more effective vaccination strategy. Fe3O4-R837 SPs efficiently synergize with PD-L1 antibody to eliminate the primary tumours and prevent tumour metastasis to lungs/liver.	[140]
Core-shell ferrite nanoparticles (CoFe2O4@MnFe2O4 nanoparticles)	Dimercaptosuccinic acid molecule	Anti-PD-L1 antibody	ICD/Immune checkpoint inhibitor	Magnetic hyperthermia induced TAAs release eliciting a systemic immune response affecting distant metastatic tumours. The combined MHT and checkpoint inhibitor demonstrate the great potentials in inhibiting the growth of both primary and metastatic tumours.	[141]
FePt/MoS2-FA nanocomposites (FPMF NCs)	FePt capped by dimercaptosuccinic acid, MoS2 modified by thiol-polyethylene glycol-folate	CpG ODN, anti-CTLA-4 antibody	ICD/Immune checkpoint inhibitor	PDT act as ICD inducer and its ability to inhibit primary tumours and prevent metastasis was significantly improved when combined with chemotherapy drug/immunotherapeutics.	[142]
Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide-bridged mesoporous organosilica bodies with magnetic heads(M-MONs@Ce6)	Asymmetric mesoporous silica growth, coated with cancer cell membrane	Anti-CTLA-4 antibody	ICD/Immune checkpoint inhibitor	The combination of PDT and magnetic hyperthermia elicits ICD, resulting in tumour-specific immune responses. When combined with anti-CTLA-4 antibody, synergistically enables the eradication of primary and deeply metastatic tumours.	[143]
Iron nanoparticles (FeNPs)	Poly(acrylic acid) (PAA) co-grafted with dopamine (DA) and amine-terminated PEG (5 kDa)	R837	ICD/Immune adjuvant/Immune checkpoint inhibitor	The combination of MNP-based MHT with local injection of nanoformulated TLR7-agonist and systemic injection of anti-CTLA4 antibody resulted in systemic immune responses that inhibited tumour metastasis and recurrence.	[144]