Table 3.

Summary of studies on the nanomaterial‐enabled drug delivery for PDAC therapy

Nanocarriers	Polymers/Macromolecules	Targeting Ligands	Drugs	Cell Lines	In vivo Models	Outcomes	Ref
Micelles	Cetuximab C225‐poly(ethylene glycol)‐block‐poly(2‐methyl‐2‐carboxyl‐propylene carbonategraft‐dodecanol (C225‐PEG‐PCD), GEM conjugated poly(ethylene glycol)‐block‐poly(2‐methyl‐2‐carboxyl‐propylene carbonate‐graft‐dodecanol‐graft‐tetraethylenepentamine) (PEG‐b‐PCC‐g‐GEM‐g‐DC‐g‐TEPA)	Cetuximab C225	GEM, miR‐205	Miapaca‐2 cells	Miapaca‐2 orthotopic tumor model	Enhance EGFR‐mediated cellular uptake, increase accumulation of C225‐micelles, increase apoptosis and reduce EMT	[ 113 ]
Micelles	Poly(ethylene glycol)‐poly(l‐/d‐ glutamate)	–	Cisplatin	BxPC3 cells	BxPC3 subcutaneous tumor model	Promote NPs accumulation and retention, improve antitumor efficacy	[ 114 ]
Micelles	Poly(styrene maleic acid)‐hyaluronic acid (SMA‐HA)	HA	3, 4‐difluorobenzylidene curcumin (CDF)	Miapaca‐2 cells, AsPC‐1 cells	–	Increase the uptake of NPs, reduce CD44 expression, inhibit NF‐KB	[ 306 ]
Polymeric NPs	Dendrigraft poly‐l‐lysine‐EGPLGVRGK‐poly(ethylene glycol)‐poly(caprolactone) (DGL‐EGPLGVRGK‐PEG‐PCL)	–	GEM	Panc‐02 cells, 4T1 cells	Panc‐02/NIH3T3 subcutaneous tumor model, 4T1/NIH3T3 subcutaneous tumor model	Increase long‐term antitumor effect	[ 132 ]
Polymeric NPs	Cell‐penetrating peptide (CPP)‐based amphiphilic peptide (C2KG2R9)‐cholesterol monomers	Human fibroblast activation protein‐α (FAP‐α) monoclonal antibody (mAb)	DOX	CAFs cells, PC‐3 cells, HUVECs	CAFs/PC‐3 subcutaneous tumor model	Enhance tumor targeting, penetration, and accumulation of various therapeutics, improve the cellular uptake and the antitumor efficacy	[ 146 ]
Polymeric NPs	Chaperonin GroEL	–	DOX	MDA‐MB‐231 cells	MDA‐MB‐231 subcutaneous tumor model, Panc‐1 subcutaneous tumor model	Effective and highly selective drug delivery without adverse effects on the major organs	[ 121 ]
Polymeric NPs	Human serum albumin (HSA)	–	Paclitaxel, tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL)	Miapaca‐2 cells	Miapaca‐2 subcutaneous tumor model	Increase apoptotic activity, improve antitumor efficacy	[ 104 ]
Polymeric NPs	Bovine serum albumin (BSA)		GEM	Miapaca‐2 cells, Panc‐1 cells	–	Enhance cellular uptake and stability of GEM, increase apoptotic activity	[ 99 ]
Polymeric NPs	Aptamer/cell‐penetrating peptide‐camptothecin prodrug	GBI‐10 aptamer	Camptothecin	Miapaca‐2 cells	Miapaca‐2 orthotopic tumor model	Enhance tumor penetration and antitumor efficacy, reduce cytotoxicity	[ 107 ]
Polymeric NPs	Poly(ethylene glycol)‐poly(d,l‐lactic acid) (PEG‐PLA)	–	Salinomycin (SAL)	AsPC‐1 cells	AsPC‐1 subcutaneous tumor model	Increase cell mortality and apoptosis, inhibit invasion and harness EMT, eradicate tumor and increase survival rate	[ 110 ]
Polymeric NPs	Fourth generation poly(amidoamine) (PAMAM) dendrimer‐HA	HA	CDF	Miapaca‐2 cells	–	Enhance cellular uptake, increase in the IC50 value improve safety and therapeutic margin	[ 115 ]
Polymeric NPs	PCL‐CDM‐PAMAM/Pt (G3, G5, G7), PEG‐PCL, PCL	–	Pt prodrug c,c,t‐[Pt(NH3)2Cl2(OH)(O2CCH2CH2CO2H)]	Panc‐02 cells, MCSs	Panc‐02 orthotopic tumor model	Balance tumor penetration, cell internalization, and tumor retention	[ 116 ]
Polymeric NPs	PEG2000‐S‐S‐PLA6000, N3‐PEG2000‐PLA6000	MMP‐7	DOX, curcumin	BxPC‐3 cells, AsPC‐1 cells	–	Facilitate the cellular internalization preferentially in the cancer cells, and subsequent nuclear transport	[ 119 ]
NPs‐Liposomes	HSA, dipalmitoylphosphatidylcholine (DPPC), Brij78	–	Ellagic acid (EA)	BxPC‐3 cells	BxPC3/HPaSteC subcutaneous tumor model	Improve drug blood retention, facilitate penetration and accumulation of NPs into tumor matrix, increase apoptosis and inhibit tumor growth	[ 133 ]
NPs‐Gels	Monomethoxy (polyethylene glycol)‐poly(d,l‐lactide‐co‐glycolide)‐poly(l‐lysine)‐cyclic peptide (arginine‐glycine‐asparticglutamic‐valine acid) (mPEG‐PLGA‐PLL‐cRGD)	cRGD	Paclitaxel	Aspc‐1 cells, Aspc‐1/PTX cells	Aspc‐1/PTX subcutaneous tumor model, Aspc‐1/PTX orthotopic tumor model	Prolong the release and elimination times, enhance the paclitaxel uptake and the antitumor effects	[ 134 ]
MSNs	DPPC, cholesterol, 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethyleneglycol)] (DSPE‐PEG)	–	Paclitaxel, GEM	Panc‐1 cells	Panc‐1 orthotopic tumor model	Enhance dual delivery carrier efficacy, increase the phosphorylated DNA‐interactive GEM metabolite, decrease the inactivated and deaminated metabolite, inhibit primary tumor growth and eliminated metastatic foci, no local/systemic toxicity	[ 127 ]
MSNs	1,2‐Distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC), cholesterol, DSPE‐PEG	–	Irinotecan	Panc‐1 cells, KPC cells	KPC orthotopic tumor model	Increase drug accumulation at tumor site, treat tumor metastases, improve PDAC survival, decrease toxicity in the gastrointestinal, liver, and bone marrow	[ 100 ]
MSNs	Cancer cell membrane	–	DOX	BxPC3 cells, human pancreatic stellate cells (hPSCs)	BxPC3/hPSCs subcutaneous tumor model	Improve immunoevasion, enhance ECM penetration, tumor accumulation, and antitumor efficacy	[ 128 ]
CdSe/ZnS QDs	MMP‐9 detachable PEG, cathepsin B‐cleavable GEM	cRGD	GEM	BxPC3 cells	BxPC3 subcutaneous tumor model	Increase the accumulation of NP in tumor tissue, enhance the tumor inhibitor activity, reduce the side effects	[ 122 ]
Iron oxide NPs	F127	–	GEM, curcumin	HPAF‐II cells, Panc‐1 cells, pancreatic cancer stem cells (CSCs)	HPAF‐II/PSCs orthotopic tumor model	Increase accumulation and uptake of NPs in tumor site, reduce metastasis and tumor growth	[ 123 ]
Iron oxide NPs	Citric acid	–	Gambogic acid	Capan‐1 cells	–	Induce apoptosis, enhance anticancer activity	[ 129 ]
Metal‐organic frameworks (MOFs)	–	–	GEM	Panc‐1 cells	–	Enhance therapeutic efficiency	[ 124 ]
Calcium phosphosilicate NPs	mPEG	–	5‐FU, GEM	Panc‐1 cells, BxPC‐3 cells	Panc‐1 orthotopic tumor model	Enhance NP/drug delivery and the uptake by tumor cells	[ 125 ]