Table 4.

Nanoparticles for brain drug delivery.

Ref	[207,208,209]	[210,211,213]	[214,215,216,218]	[221,222]	[227,228]	[230,233,234] [231,235]
Examples	AAV9-hIFNβ, retroviral herpes simplex virus-thymidine kinase (HSV-tk), Toca 511 delivers suicide gene, cytosine deaminase (CD), and in combination with oral prodrug, adenoviral vector carrying the wild-type p53 gene (Ad-p53)	Paclitaxel with bEND.3 cell-derived exosome, doxorubicin with U-87 MG cell-derived exosome, miRNA-486-5p transferred exosomes, siKrasG12D iExosomes, tumor-cell-derived exosomes and α-GalCer on a DC-based vaccine	Neutrophil-mediated paclitaxel cationic liposomes, carboxylesterase-expressing allogeneic neural stem cells, bone morphogenetic protein 4 (BMP4) expressing adipose-derived mesenchymal stem cells, neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL)	Iron oxide nanoparticles, gold nanoclusters, mesoporous silica nanoparticles, lanthanide upconversion particles	Cationized bovine serum albumin modified NPs, polysorbate 80 or poloxamer 188 overcoated NPs, apolipoprotein bound nanoparticles,	Transferrin receptor-targeted (OX26) immunoliposomes, LDLR-DHA nanoparticles, insulin-mAb-modified HSA NPs; Glutathione-modified liposomes, choline-derivate-modified NPs
Disadvantages	i. Limited brain tumor penetration ii. Highly invasive administration method iii. Prevailing risk of oncogenesis and lethality	i. Lacking standardized isolation and purification procedure, ii. Donor cells choice iii. Potential tumor induction risk of tumor cell-derived exosomes	i. Potentially toxic effects of the cargo on the cell carrier itself ii. Spatial and temporal release of the therapeutic agent iii. Limited loading efficiency	i. Neurotoxicity ii. Unspecific distribution	i. Poor selectivity ii. Protein adsorption and corona formation	i. Protein adsorption and corona formation ii. Potential neurotoxicity iii. Difficulty of manufacturing
Advantages	i. High efficiency for gene delivery, ii. Innate ability to infect cells	i. Nonimmunogenic ii. Stable and long circulation iii. Cross BBB iv. Target the tissue via their natural surface proteins	i. Cross BBB ii. Naturally recruited to sites of brain tumors	i. Ultrasmall size ii. Easily modified iii. Contrast imaging iv. Phototherapeutics	i. Electrostatic adsorption ii. Improve cellular uptake iii. Improve penetrating efficiency	i. High selectivity ii. Enhanced brain accumulation iii. Cross BBB iv. Decrease systemic toxicity
Strategy					AMT	RMT and TMT
	Viral vectors	Exosomes	Cell carriers	Passive diffusion	Actively targeted delivery
	Biological vectors			Synthetic vehicles