Table 1.

Nanoparticle protein kinase inhibitor delivery targeting pathways involved in therapy resistance

Nanoparticle type	Active targeting	PKI	Primary kinase targeted	Other compounds	Model	References
Accurin polymer based	–	AZD2811	Aurora B kinase		Human colon cancer	[83]
Glutaraldehyde crosslinked albumin	Anti-EGFR nanobodya	17864 (platinum-bound sunitinib analog)	PDGF-R/VEGFR		Human head and neck squamous cell carcinoma (in vitro)	[84]
Gold	–	Erlotinib	EGFR		Human adenocarcinoma and non-small-cell lung cancer (in vitro)	[85]
Gold	Anti-EGFR antibody a	Gefitinib	EGFR		Lung cancer (in vitro)	[86]
Hexadentate-PLGA	–	PD98059	MEK	Cisplatin (not in nanoparticle)	Melanoma and lung carcinoma	[36]
Iron oxide/magnetite	–	AM-005 + AT-9283	Aurora kinase		Liver cancer	[87]
Liposomal	–	WHI-131	JAK3/EGFR		Human B-lineage ALL/breast cancer	[88, 89]
Liposomal	−/Anti-CD19 antibody a	SYK-P-site inhibitor C61	SYK		B-precursor acute lymphoblastic leukemia	[90–92]
Liposomal	Anti-EGFR nanobody a	AG538	IGF-1R		Human head and neck squamous cell carcinoma and breast adenocarcinoma	[42]
Liposomal	Folate	Erlotinib	EGFR	Doxorubicin	Human breast and lung cancer	[38]
Liposomal (layer-by-layer)	CD44a	Selumetinib + PX-866	MEK1/2 + PI3 K		Human breast cancer	[93]
Oleic acid based	–	AZD6244	MAPK	Cisplatin	Human cervical/breast/liver cancer (in vitro)	[94]
PLGA-PEG di-block copolymer	–	Wortmannin	PI3 K	Docetaxel	Human lung and prostate cancer	[39]
PLGA	–	LY294002	PI3 K		Murine melanoma and human breast cancer	[95]
Reverse micelles	–	Erlotinib	EGFR		Pancreatic adenocarcinoma (in vitro)	[96]

EGFR epidermal growth factor receptor, IGF-1R insulin-like growth factor 1 receptor, JAK3 Janus kinase 3, MEK mitogen-activated protein kinase, PDGF-R platelet-derived growth factor receptor, PI3K phosphoinositide 3-kinase, PLGA poly(lactic-co-glycolic acid), SYK Spleen tyrosine kinase, VEGFR vascular endothelial growth factor receptor

^aActivate targeting with dual role: (1) NP targeting moiety and (2) direct perturbing mechanism of resistance by receptor agonism/antagonism or may trigger antibody mediated cytotoxicity