Table 2.

Exosomes derived from different cell sources that are involved in brain cancer treatment.

Cell Source	Encapsulated Cargo		Outcome In Vitro	Outcome In Vivo	Reference
	Macromolecule	Drug
Mesenchymal stem cell-derived exosomes	yCD::UPRT	5-FC	Tumor growth inhibition of C6 GBM cells		[199]
	miR-124 and miR-145	n.p.	Reduced migration rate of tumor cells and diminished the regeneration capacity of GSCs	U87-derived xenograft penetration and downregulation of miR-124 target genes, such as CDK6	[200]
	Anti-miR-9	n.p.	Chemosensitivity, increased cell death as well as elevated caspase activity	n.s.	[201]
	miR-512-5p	n.p.	Cell propagation inhibition and cell cycle arrest induction	n.s.	[202]
	miR-199a	n.p.	Suppression in proliferation, invasion and migration as well as TMZ chemosensitivity induction	Repression of tumor growth	[203]
	miR-29a-3p	n.p.	Migration and vasculogenic mimicry formation attenuation		[204]
	miR-133b	n.p.	Suppression in proliferation, invasion and migration	n.s.	[205]
	miR-584	n.p.	Decreased proliferation and invasion rate of glioma cells	Attenuation of malignant gliomas development	[206]
	miR-146b	n.p.	n.s.	Glioma xenograft growth inhibition	[207]
	n.p.	n.p.	Apoptosis induction in C6 cells	n.s.	[208]
	STAT3-siRNA	TMZ	Inhibition of TMZ-resistant GBM growth		[209]
	miR-124a	n.p.	Significant reduction in viability and clonogenicity of GSCs	Tumor growth retention and increased survival	[210]
	n.p.	Atorvastatin	Reduced cell propagation, migration and VEGF secretion as well as increased apoptotic activity	n.s.	[211]
	n.p.	Atorvastatin	Tumor growth suppression in a 3D GBM model	n.s.	[212]
	GPX4-siRNA	BQR	Enhanced ferroptosis in GBM cell lines	BBB penetration and tumor-targeting ability	[213]
	miR-375	n.p.	Inhibition in cell propagation, migration and infiltration as well as apoptosis induction	Repression of xenograft tumor in nude mice	[214]
	lncRNA PTENP1	n.p.	Suppression of malignant phenotype of U87 cells	n.s.	[215]
	n.p.	DOX	Increased cytotoxicity against cancer cells	n.s.	[216]
	Cytosine deaminase and miR-34a	n.p.	Increased apoptosis	n.s.	[223]
	FGFR3-TACC3 siRNA	n.p.	Decreased cell viability	Improved survival in glioma-bearing mice without toxicity to adjacent normal tissues and affecting the wild-type FGFR3 or TACC3	[225]
Embryonic stem cells-derived exosomes	n.p.	PTX	Improvement in the therapeutic effects of PTX through optimized targeting	n.s.	[219]
Neural stem cells-derived exosomes	STAT3 ASOs	n.p.	Stimulation of the immunogenic activity of human dendritic cells or mouse macrophages	Inhibit growth of GL261 tumors	[228]
	miR-124-3p	n.p.	Glioma cell proliferation, migration, and invasion as well as FLOT2 expression suppression	Tumor growth inhibition in a mouse tumor xenograft model	[229]
Macrophage-derived exosomes	miR-21	DOX	High apoptotic effect in glioma cells	n.s.	[231]
	n.p.	Curcumin	Targeted imaging and curative effects with reduced side effects		[232]
	Catalase	ICG	Relief of the intracellular hypoxia microenvironment	BBB penetration, brain accumulation ability and strong anticancer effect	[233]
	n.p.	n.p.	n.s.	100% Mice survival ratio	[234]
	O6-benzylguanine (BG)	TMZ	Proliferation inhibition of U87MG and GSCs	n.s.	[235]
	PPM1D-siRNA	Panobinostat	DIPG cell proliferation inhibition	n.s.	[236]
	circBTG2	n.p.	Inhibition in cell proliferation and invasion	n.s.	[237]
	miR-15a and miR-92a	n.p.	Inhibition of malignant behavior of glioma cells	n.s.	[238]
	n.p.	DOX	Tumor growth suppression		[239]
Glioma cells-derived exosomes	n.p.	HCQ	High antitumor potency with visible light illumination		[217]
	n.p.	ICG	n.s.	Abolishment of tumor growth	[240]
	n.p.	TMZ and DHT	Good antitumor efficacy and targeting of the tumor site of TMZ-resistant cells and mice models		[241]
	miR-151a	n.p.	chemosensitivity recovery to TMZ		[242]
	n.p.	Selumetinib	Strong antitumor effect	Strong antitumor effect with zero toxicity	[243]
	n.p.	PTX	High cytotoxicity to U87 and T98G cell lines	n.s.	[244]
	miR-7-5p	VB	Inhibition of cell proliferation, invasion, and migration as well as vessel-like tube formation	Diminish tumor formation and metastasis	[245]
	n.p.	DOX and PTX	Autologous exosomes represent the most potent weapon for glioma drug targeting	n.s.	[246]
	[Ag (GSH)]+	DOX	High glioma cells uptake and constant DOX release in cancerous cells	n.s.	[247]
	alpha-Galactosylceramide	n.p.	n.s.	Stimulation of tumor-specific cytotoxic T lymphocytes proliferation, synergistically breaking the immune tolerance and improving the immunosuppressive environment	[248]
Blood exosomes	n.p.	DOX	Neoplastic growth suppression		[239]
	PTEN mRNA	n.p.	n.s.	Restoration of tumor suppression, enhancement of tumor growth inhibition, and improvement of survival in an orthotopic PTEN-deficient glioma mouse	[249]
	n.p.	DOX and miR-21i	Acceleration of the endocytic uptake and enhanced tumor accumulation ability	Improved and synergistic antitumor effect	[250]
	n.p.	TanIIA and GL	Great BBB penetration and apoptosis inducement in GL261 cells	Extension of mice median survival and when co-administered with TMZ, a synergistic therapeutic effect was recorded as well as inhibition of postoperative recurrence	[251]
	cPLA2-siRNA	Metformin	Increased cellular uptake and strong antitumor effect	Inhibition of tumor growth and significant extension of mice survival time	[252]
Natural brain endothelia cell-derived exosomes	VEGF-siRNA	n.p.	BBB penetration efficiency and increased cellular uptake	Strong BBB penetration and aggregation abortion of xenotransplanted cancer cells	[257]
	n.p.	DOX & PTX	High cytotoxicity and intracellular uptake to U87 cell line	Efficient BBB penetration	[255]
293T cell-derived exosomes	AMO-21	n.p.	Increased delivery efficiency to C6 GBM cells	Expression induction of PDCD4 and PTEN as well as tumor shrinkage	[258]
	miR-21-sponge construct	n.p.	Cell proliferation reduction and increased apoptosis	Tumor growth retention and tumor retardation inducement as well as reduction in tumors volume	[259]
	n.p.	DOX	Increased apoptosis	Life expectancy extension and antitumor activity enhancement	[253]
	n.p.	Cur/ STAT3-inhibitor	n.s.	Abortion in tumor growth and mice survival increase	[254]
Milk exosomes	siRNA against a plethora of oncogenes	n.p.	Knockdown of oncogenes and reduced cell proliferation	n.s.	[260]

n.p.: not present; n.s.: not studied.