Table 3.

Examples of engineering exosomes for brain targeting and delivery

Carrier proteins	Method of engineering	Cargo	Effect	Reference
T7-Lamp2b (HAIYPRH, T7)	genetic engineering	antisense miR-21 (AMO-21)	target delivery AMO-21 into intracranial GBM	Kim et al.95
CD9-ApoB	genetic engineering	N/A	prolong retention in the brain	Tian et al.104
RVG-LAMP-2B	genetic engineering	BACE1 siRNA	directing BACE1 siRNA to brain neurons with great potential for AD therapy	Cui et al.86
	genetic engineering	HMGB1-siRNA	higher brain accumulation, effective gene silence in ischemic strokes.	Kim et al.88
	genetic engineering	miR-124	promotes gene-drug delivery to the ischemic cortex of the brain and attenuates ischemic damage	Yang et al.87
	genetic engineering	opioid receptor mu (MOR) siRNA	delivery of siRNA to the central nervous system and restrain the morphine relapse	Liu et al.105
	genetic engineering	mRNA (e.g., nluc, catalase)	deliver cargo mRNA to the brain, rescues neurotoxicity and neuroinflammation in Parkinson’s disease	Kojima et al.106
	genetic engineering	circDYM	ameliorates depressive-like behaviors	Yu et al.90
	genetic engineering	circSCMH1	enhance functional recovery in both rodent and nonhuman primate ischemic stroke models	Yang et al.91
	genetic engineering	nerve growth factor protein and mRNA	simultaneous delivery of nerve growth factor mRNA and protein to the ischemic cortex	Yang et al.92
	genetic engineering	BM-MSC exos	targeted MSC-derived exosomes to cortex and hippocampus rescue memory deficits in AD mouse	Xin et al.77
	genetic engineering	aptamer F5R1 or F5R2	decrease the α-synuclein aggregates in the PD model	Ren et al.93
	genetic engineering	MSC-exosome	regulate neuroinflammatory responses in the AD brain	Cui et al.86
RVG-CP05	anchor peptide	RVG-CP05	exosomal anchor peptide enables direct functionalization of exosomes for brain-targeted delivery	Gao et al.107
CXCR4	genetic engineering	MSC-exosome	enhances the delivery of exosomes to the ischemic brain tissue	Li et al.101
	genetic engineering	TRAIL	anti-brain metastases of breast cancer	Liu et al.102
RGD-C1C2 (ACDCRGDCFC, RGD)	genetic engineering	neural progenitor cell-exosome	target the lesion region of the ischemic brain and anti-inflammatory activity	Gao et al.107
c(RGDyK) peptide (Arg-Gly-Asp-D-Tyr-Lys)	bio-orthogonal copper-free click chemistry	MSC-exosome, curcumin	target ischemic tissue, anti-inflammatory approaches to ischemic stroke	Tian et al.104
c(RGDyK) peptide	bio-orthogonal copper-free click chemistry	MSC-exosome, miR-210	targeted delivery to the ischemic brain, regulate angiogenesis in ischemic brain injury	Zhang et al.108
NRP-1 targeted peptide (RGERPPR, RGE)	click chemistry	superparamagnetic iron oxide nanoparticles, curcumin	brain-targeted imaging and treatment of glioma	Jia et al.109
Angiopep-2 (TFFYGGSRGKRNNFKTEEY, An2)	–	signal transducers and activators of transcription 3 siRNA	crossed the BBB and targeted to glial cells, enhanced GBM’s median survival rate	Liang et al.110
Angiopep-2; CD133 RNA aptamers	amphiphilic molecule bridge	temozolomide, O6-benzylguanine	dual targeting effect of exosomes, anti- GBM properties	Liang et al.111
Angiopep-2	DSPE-PEG2000-Angiopep-2	docetaxel	targeted brain-tumor drug delivery and therapy	Wu et al.112
Iron oxide nanoparticles	physical engineering	–	accumulate to the ischemic lesion, promote anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion	Kim et al.113