Table 3.

Nanoparticle (multiple) compound delivery targeting pathways involved in therapy resistance

Nanoparticle type	Active targeting	Compounds	Primary method of resistance targetedb	Model	References
Amphiphilic polymer	–	Curcumin + doxorubicin	ABC pumps/NF-κB	Human multiple myeloma, acute leukemia, prostate and ovarian cancers	[74]
Cationic amphiphilic copolymer	–	IL12 plasmid + Paclitaxel	Immune suppression	Murine breast cancer	[118]
Chitosan based	–	Curcumin + doxorubicin	ABC pumps/NF-κB	Human breast cancer (in vitro)	[75]
Dendrimer	Transferrin receptor-specific peptide	TRAIL + doxorubicin	FADD	Human liver cancer	[119]
Flaxseed oil emulsion	–	Curcumin + paclitaxel	ABC pumps/NF-κB	Human ovarian adenocarcinoma (in vitro)	[120]
Gel-liposome	Hyaluronic acid	TRAIL + doxorubicin	FADD	Human breast cancer	[121]
Graphene	–	TRAIL + doxorubicin	FADD	Human lung cancer	[122]
Lipid	–	Curcumin + doxorubicin	ABC pumps/NF-κB	Human liver cancer	[123]
Liposomal	RGDK-lipopeptide	Curcumin + doxorubicin	ABC pumps/anti-angiogenic	Murine melanoma	[124]
Liposomal	DQA	Lonidamine + epirubicin (in a separate liposomal formulation)	Mitochondrial hexokinase 2	Human lung cancer	[125]
Liposomal	–	TRAIL + doxorubicin (in separate nanoparticles)	FADD	Human lung cancer	[126]
Liposomal (plus [D]-H6L9)	–	MiR-10b + paclitaxel	RhoC	Murine breast cancer	[127]
Liposomal (plus MG)	Her-2 antibody	Verapamil + doxorubicin	P-glycoprotein	Human breast cancer	[128]
Micellar based	–	Curcumin + doxorubicin	ABC pumps/NF-κB	Murine lung cancer	[129]
Micellar based	–	Disulfiram + Doxorubicin	P-glycoprotein	Human breast cancer	[130]
PCDA based	Biotin	Curcumin + doxorubicin	P-glycoprotein	Human breast cancer	[131]
PLGA based	EGFR-peptide	Paclitaxel + lonidamine	Mitochondrial hexokinase 2	Human breast and ovarian cancer	[132, 133]
PLGA	–	Cyclosporin A + doxorubicin	P-glycoprotein	Human lung cancer	[66]
PLGA	Anti-EGFR antibodya	Rapamycin	mTOR	Human breast cancer (in vitro)	[134]
PLGA	Folate	Nutlin-3a + curcumin	ABC pumps/NF-κB	Human retinoblastoma (in vitro)	[135]
PLGA	–	HPI-1 + Gemcitabine (Gemcitabine not in nanoparticle)	Hedgehog/Smo	Murine medulloblastoma, human pancreatic and liver cancer	[136, 137]
PLGA	–	Curcumin + doxorubicin	ABC pumps/NF-κB	Human chronic myelogenous leukemia (in vitro)	[138]
PLGA	Biotin	Tariquidar + paclitaxel	P-glycoprotein	Murine mammary tumor	[139]
PLGA	iRGD	Camptothecin + TRAIL plasmid	FADD	Human colon cancer	[140]
PLGA	Anisamide	Resveratrol + doxorubicin	ABC pumps/NF-κB	Human breast cancer	[141]

DQA dequalinium, FADD Fas-associated protein with death domain, MG Malachite green carbinol base, FADD Fas-associated protein with Death Domain, PCDA Poly(curcumin-dithiodipropionic acid), PLGA Poly(lactic-co-glycolic acid), RhoC Ras homolog gene family, member C, TRAIL tumor necrosis factor-related apoptosis-inducing ligand

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

^bThe described inhibitor mode of action is pleiotropic and may have several targets other than described