Table 2.

Nanoparticles for regulating TIME and improving immunotherapy.

Nanoparticles	Immunotherapy	Targeting	Payload	Mechanism	Advantages	Ref
Liposome	PDT + ICB	PD-L1	IR775, metformin	PDT induces ICD; metformin downregulates PD-L1	Codelivery of hydrophilic and hydrophobic drugs	(125)
Liposome	Cytokines	TAMs	Resiquimod	TLR7/8 agonists repolarize TAMs	Administered intraperitoneally selective accumulation in TAMs	(7)
Liposome	ICB	Tregs	Indoximod prodrug, mitoxantrone	Indoximod inhibits the IDO-1 pathway and Treg expansion; mitoxantrone induces ICD	Codelivery of hydrophilic and hydrophobic drugs	(126)
Acid-sensitive polymeric nanoparticles	ICB + PDT	PD-L1	siPD-L1, carboplatin prodrug, digitoxin	Carboplatin prodrug initiates the caspase cascade; digitoxin elicits ICD; PD-L1 silencing overcome immune suppression	Environmentally responsive release and escape from the endocytic pathway	(127)
Biodegradable polymeric nanoparticles	Cytokines	TAMs	IRF5/IKKβ encoding mRNAs	IRF5 induces macrophage polarization; IKKβ activates IRF5	Reprogramming TAMs and safety for repeated dosing	(128)
PLG-g-mPEG nanoparticles	Cytokines	TAMs	Cisplatin, Resiquimod	TLR7/8 agonists repolarize TAMs	Passive targeting and drugs codelivery	(129)
Fusogenic lipid-coated MSNP	Repolarize TAMs	TAMs, PI3k	siRNA against PI3kγ, peptide LyP-1	Peptide LyP-1 targets TAMs; PI3kγ downregulation reprograms TAMs	Extremely high gene load and transfection efficiency, selective homing and transfection, avoidance of the endocytic pathway	(130)
Folic acid modified MSNP	Cytokines	T cells and DCs	CCL2	CCL2 recruits immune cells into the tumor tissue	Selective target-localizing ability and safety	(131)
SNPs	Repolarize TAMs	TAMs	/	Relatively large (>100 nm) anionic nanoparticles administered intraperitoneally selectively accumulate TAMs	Administered intraperitoneally selective accumulation in TAMs	(132)
Ferumoxytol capped ultra-large pore MSNP	ICB	PD-1	Anti-PD-1 antibody	Immune checkpoint inhibition	Sustained release and improved tumor specificity of ICIs	(133)
Copper chalcogenide nanoparticles	ICB + PTT	PD-1	Anti-PD-1 antibody, TLR9 agonist CpG	PTT induces ICD; TLR9 agonist CpG elicits activation of innate immune cells and adaptive immunity	Photothermal therapy with high penetration depth	(134)
Fe3O4 nanoparticles coated with a hybrid membrane consisting of ID8 ovarian cancer cell membrane and red blood cell membrane	PTT + PDT	/	Indocyanine green (ICG)	PTT induces ICD; red blood cell membrane coating improves the circulation time and stability; ID8 OC cell membrane coating support homologous homing properties	Prolonged circulation lifetime and high tumor specificity	(135)
Targeting peptide-modified gold nanoparticles	Inhibit TAMs	TAMs	siRNA against VEGF	siRNA inhibits the VEGF pathway in M2 TAMs and tumor cells, stimulating a host immune response	Selective gene silencing	(136)