Table 2.

Application of immune cell-based DDS in glioma

Immune cells	Components	Loaded drugs/nanoparticles	Methods	Model in vivo	Functions	References
Monocyte	Cell	Conjugated polymer nanoparticles	Trojan horse	GL261 orthotopic gliomas mice model	Target BBB and tumor Increase the PDT treatment efficacy	[86]
Monocyte	Cell	Nano-DOX	Trojan horse	Orthotopic GBM xenografts mice model	Target BBB and tumor cells Induce tumor cell damage by promoting DAMP emission	[87]
Macrophage	Cell	Photothermal nanoprobe (MFe3O4-Cy5.5)	Trojan horse	C6 orthotopic gliomas rat model	Target BBB and tumor, and penetrate deeply Perform fluorescence, photoacoustic, and magnetic resonance imaging Induce local photothermal therapy Inhibit the recurrence of glioma after surgery	[88]
Macrophage	Cell	C6/Dir loaded nanoparticles	Trojan horse	U87 orthotopic gliomas mice model	Target BBB and tumor Promote deeper permeation in tumor tissue	[89]
Macrophage	Cell	Dox	Trojan horse	–	Enhance drug release efficacy from macrophage by photochemical internalization	[90]
Macrophage	Cell	β-Glucans prodrug nanoparticles	Trojan horse	ALTS1C1 and LCPN orthotopic gliomas mice model	Target BBB and tumor cells Glutathione responsive drug release Suppress tumor growth and prolong survival time	[91]
M2 macrophage	Cell	Nano-DOX	Trojan horse	Orthotopic GBM xenografts mice model	Target BBB and tumor Modulate tumor immune microenvironment Suppress tumor growth	[92]
M1 macrophage	Cell	DOX-loaded PLGA nanoparticles	Trojan horse	U87 intracranial glioma-bearing mice model	Target BBB and tumor cells Induce tumor cell apoptosis Suppress tumor growth and prolong survival time	[93]
Macrophage	Membrane	MnO2 and cisplatin-loaded redox-responsive poly(N-vinylcaprolactam) nanogels	Hypotonic lysis/freeze–thaw/centrifugation Co-extrusion	C6 orthotopic brain glioma model	Target BBB Deplete excess glutathione Exhibit magnetic resonance imaging-guided chemotherapy/chemodynamic therapy	[94]
Macrophage	Membrane	DSPE-PEG-loaded IR-792 nanoparticles	Lysis buffer, sonication, and centrifugation Co-extrusion	U87L orthotopic GBM model	Target BBB and tumor Suppress tumor growth and prolong survival time	[95]
PD-1 overexpressed macrophage	Membrane	RAPA-loaded PLGA nanoparticles	Homogenization and centrifugation Co-extrusion	C6-Luc orthotopic gliomas mice model	Target BBB and the tumor microenvironment Block the immune checkpoint Activate the CD8+ CTL	[96]
M1-macrophage	Extracellular vesicles	CPPO and Ce6 modified and hypoxia-activated prodrug AQ4N	Incubation, ultracentrifugation, incubation and ultrafiltration (Pre-and post-loading)	Orthotopic gliomas mice model	Target BBB and tumor cells Modulate the immunosuppressive tumor microenvironment The chemiexcited photodynamic therapy and hypoxia-activated chemotherapy	[97]
Macrophage	Exosomes	SPIONs) and Cur	Differential centrifugation and ultrafiltration; Electroporation (post-loading)	U251 orthotopic gliomas mice model	Target BBB and tumor	[98]
Functionalized macrophage	Exosomes	Panobinostat and PPM1D-siRNA loaded positively charged micelles	Centrifugation and ultrafiltration; Hypotonic lysis Co-extrusion	Orthotopic DIPG-bearing mice	Target BBB and tumor Suppress tumor growth and prolong survival time	[99]
Microglia	Cell	PTX loaded liposome	Trojan horse	U87 MG and GL261 orthotopic gliomas mice model	Target BBB and tumor Transport drug to glioma cells via extracellular vesicles and tunneling nanotubes Suppress tumor progression	[100]
Microglia	Membrane	ZOL loaded nanoparticle	Mechanical crushing; Co-extrusion	GL261/TR orthotopic gliomas mice model	Target BBB and tumor cells Inducing apoptosis and inhibiting the migration and invasion of temozolomide-resistant GBM cells Improve the immunosuppressive and hypoxic microenvironment	[101]
Microglia	Membrane	Fe3O4-siPD-L1	Hypotonic lysis/freeze–thaw/centrifugation; Sonication and co-exclusion	Luc-GL261/TR orthotopic gliomas mice model	Target BBB and tumor cells Increase effector T cells and M1-type microglia Induce ferroptosis of GBM cells and maturation of DC cell Suppress tumor growth and prolong survival time	[102]
Neutrophil	Cell	PTX loaded cationic liposome	Trojan horse	Glioma surgical resection model	Target inflamed regions in brain and tumor cells Inflammatory responsive drug release Suppress the recurrence and improve survival rates	[103]
Neutrophil	Cell	DOX-loaded magnetic mesoporous silica nanoparticles	Trojan horse	Glioma surgical resection model	Target inflamed regions in brain and tumor cells Suppress tumor growth and prolong survival time Promote tumor cells and TAM apoptosis	[104]
Neutrophil	Cell	Escherichia coli membrane-enveloped, PTX-loaded magnetic nanogels	Trojan horse	Glioma surgical resection model	Target inflamed regions in brain and tumor cells Inhibit the proliferation of tumor cells	[105]
Neutrophil	Cell	PTX and anti-PD-1 antibody-loaded nanosensitizer	Trojan horse	GL261 tumor-bearing C57BL/6 mice	Target inflamed regions in brain and tumor cells Ultrasound responsive drug release Kill tumor and induce local inflammation Improve survival rates	[106]
Neutrophil	Exosomes	DOX	Centrifugal and filter separation, Sonication, and incubation (post-loading)	Zebrafish and C6-Luc glioma-bearing mice models	Target BBB and tumor cells Suppress tumor growth and prolong survival time	[107]
Neutrophil/ Macrophage	Membrane	RAPA-loaded PLGA nanoparticles	Hypotonic lysis and homogenizer; Sonication and co-extrusion	C6-Luc glioma-bearing mice models	Target inflamed regions in brain and tumor cells Eliminating glioma cells and inducing durable tumor regression	[108]
NK cell	Membrane	AIE nanoparticles	Lysis buffer/differential ultracentrifugation and co-extrusion	Orthotopic glioma models	Target BBB and tumor cells Trigger TJs disruption and actin cytoskeleton reorganization Suppress tumor growth	[109]
DC cell	Cell	Nano-DOX	Trojan horse	Orthotopic human GBM xenografts mice model	Target BBB and tumor Enhance DC-driven anti-GBM immune response	[110]
DC cell	membrane	RAPA-loaded PLGA nanoparticles	Lysis buffer and centrifugation Co-extrusion	C6-Luc glioma C57 mice	Target BBB and tumor Enhance immune response Suppress tumor growth and prolong survival time	[111]
DC cell	C6 and DC membrane	DTX nanosuspensions	Hypotoniclysis/freeze–thaw/differential ultracentrifugation and sonication	Intracranial glioma- mouse model	Target BBB and tumor Enhance DTX anti-tumor efficiency Activate downstream immune system	[112]

AIE aggregation-induced emission, BBB blood–brain barrier, CPPO bis(2,4,5-trichloro-6-carbopentoxyphenyl) oxalate, CTL cytotoxic T-lymphocyte, Cur curcumin, DAMP damage-associated molecular patterns, DC dendritic cell, DIPG diffuse intrinsic pontine glioma, Dir 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine Iodide, DOX doxorubicin, DSPE-PEG 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000], DTX docetaxel, C6-Luc C6 glioma cells that luciferase reporter-gene labeled, GBM glioblastoma, PD-1 programmed cell death-1, PDT photodynamic therapy, PLGA poly(lactic-co-glycolic acid), PPM1D protein phosphatase 1, PTX paclitaxel, RAPA Rapamycin, SPIONs superparamagnetic iron oxide nanoparticles, TAM tumor-associated macrophages, TJs tight junctions, ZOL Zoledronate. “–” represent no mentioned