Polyphenols delivery by polymeric materials: challenges in cancer treatment

Figures & data

Figure 1. Chemical structure of main polyphenols of biological relevance.

Figure 2. Molecular mechanisms of the biological action of EGCG on tumor cells.

Table 1. Composition and activity of main polyphenol nanocarriers employed in cancer therapy.

			Polyphenol
Carrier					Anticancer activity
Type	Composition	Preparation	Type	Cancer type	Cells	Synergism	In vivo model	References
NPs	PLGA-PEG	ESE	PmPs	Breast	MCF-7, Hs578T	–	–	Shirode et al. (2015)
NPs	CT	IG	TPs	Hepatic	HepG2	–	–	Liang et al. (2014)
NPs	CT	IG	TPs	Hepatic	HepG2	–	–	Liang et al. (2011)
NF	PCL	ESP	PPs	Gastric	MKN28	–	–	Kim et al. (2012)
NPs	ALG-CT-PX F127	IG	CUR	Cervice	HeLa	–	–	Das et al. (2010)
NPs	PLGA	ESE	CUR	Oral	CAL27	–	–	Chang et al. (2013a)
NPs	FB	CaCl2 CK	CUR	Prostate	PC3	–	–	Sanoj Rejinold et al. (2011)
				Breast	MCF-7
NPs	PLGA	ESE	CUR	Prostate	LNCaP, PC-3, DU-145	–	–	Mukerjee & Vishwanatha (2009)
NPs	PLGA	ESE	CUR	Osteosarcoma	U2OS	–	–	Peng et al. (2014)
HYs	CHT	IG	CUR	Melanoma	A375	–	–	Mangalathillam et al. (2012)
NPs	Peptide	SA	CUR	Medulloblastoma	DAOY	–	–	Altunbas et al. (2011)
NPs	NIPAA-VP-PEG-MA	RP	CUR	Pancreas	MiaPaCa2, Su86.86, BxPC-3, Capan-1, PANC-1, E3LZ10.7, PL-5, PL-8	–	HM	Bisht et al. (2007)
NPs	CT-PBCA	EP	CUR	Hepatic	HepG2, Bel7402, Huh7	–	HepG2 XM	Duan et al. (2010)
HYs	PX 407–PX F188	SA	CUR	Melanoma	B16-F10	–	–	Sun et al. (2014b)
NPs	CL	NPR	CUR	Prostate	C4-2, LNCaP, DU-145, PC-3	–	–	Yallapu et al. (2012)
NPs	PLGA	ESE	CUR	Cervice	HeLa	–	–	Nair et al. (2012)
NPs	PLGA–PX F127	NPR	CUR	Cervice	KB-V1, KB-3-1	–	–	Punfa et al. (2012)
HYs	PEG-DA-AA	RP	CUR	Cervice	HeLa	–	–	Deepa et al. (2012)
HYs	FA-PEG-DA-AA	RP	CUR	Cervice	HeLa	–	–	Pillai et al. (2014)
NPs	PLGA	NPR	CUR	Ovarian	A2780, A2780CP	–	–	Yallapu et al. (2010a)
NPs	PLGA-PEG	ROP	CUR	Breast	MCF-7	–	–	Mirakabad et al. (2016)
NPs	PLGA	ESE	CUR	Breast	MCF-7	–	–	Verderio et al. (2013)
NPs	EU-S100	ESE	CUR	Colon	HT-29	–	–	Prajakta et al. (2009)
NPs	PLGA-PEG	NPR	CUR	Colon	HT29	–	HM	Li et al. (2014)
NPs	HSA	ESE	CUR	Colon	HCT116	–	HCT116 XM	Kim et al. (2011)
				Pancreas	MiaPaCa2
HYs	CT, GL, HA	EFS	CUR	Lung	A549	–	–	Teong et al. (2015)
NPs	NIPAA-VP-AA	RP	CUR	Medulloblastoma	DAOY, D283Med	–	–	Lim et al. (2011)
				Glioblastoma	HSR-GBM1, JHH-GBM14
HYs	CT	IG	CUR	Oral	SCC25	–	–	Popat et al. (2014)
NPs	PLGA	NPR	CUR	Prostate	DU-145, PC-3	–	XM	Yallapu et al. (2014)
HYs	GL-PAGA	EP	CUR	Colon	HCT-116	–	–	Madhusudana Rao et al. (2015)
NPs	PLGA	ESE	CUR	Breast	MCF-7	5-FU	–	Balasubramanian et al. (2014)
NPs	CT-PBCA	EP	CUR	Breast	MCF-7	DOX	–	Duan et al. (2012)
NPs	PLGA	NPR	CUR	Ovarian	A2780CP	CP	–	Yallapu et al. (2010b)
				Breast	MDA-MB-231
NPs	NIPAA-VP-AA	RP	CUR	Pancreas	–	GM	Pa03C XM	Bisht et al. (2010)
NPs	GL-PEC	LbL	EGCG	Breast	MBA-MD-231	–	–	Shutava et al. (2009)
NPs	CS-pp-CT	GP-CK	EGCG	Hepatic	HepG2	–	–	Hu et al. (2014)
				Gastric	BGC823
NPs	CS-pp-CT	GP-CK	EGCG	Colon	Caco-2	–	–	Hu et al. (2015)
NPs	PLGA-PEG	NPR	EGCG	Prostate	LNCaP	–	–	Sanna et al. (2011)
NPs	HA	SA	EGCG	EAC	EAC	DOX	–	Ray et al. (2013)
NPs	CT	IG	EGCG	Melanoma	Mel928	–	Mel928 XM	Siddiqui et al. (2014)
NPs	PLGA-PEG	NPR	EGCG	Prostate	PC-3	–	22Rυ1 XM	Siddiqui et al. (2009)
NPs	CT	IG	EGCG	Prostate	–	–	22Rυ1 XM	Khan et al. (2014)
NPs	CT-GL-PEG	IG	EGCG	Gastric	Luc MKN45	–	XM	Lin et al. (2015)
NPs	PLGA	NPR	EGCG	Lung	A549	CP	–	Singh et al. (2011)
				Cervice	HeLA
			TF	Leukemia	THP-1
NPs	PLGA	SE	EGCG	Lung	A549	CP	EAC XM	Singh et al. (2015)
				Cervice	HeLA
			TF	Leukemia	THP-1
				EAC	–
NPs	BSA	NPR	RV	Lung	NCI-H460	–	–	Karthikeyan et al. (2015)
NPs	BSA	NPR	RV	Ovarian	SKOV3	–	–	Guo et al. (2015)
NPs	PLGA	EM	RV	Breast	MCF-7	–	–	Kumar et al. (2016)
NPs	PLGA-PEG	NPR	RV	Prostate	DU-145, LNCaP	–	–	Sanna et al. (2013)
NPs	MI-PEG-PLA	SA	RV	Glioblastoma	CT26, U87	–	CT26 XM	Guo et al. (2013)
NPs	CT	IG	Q	Pancreas	MiaPaCa2,	5-FU	–	David et al. (2015)
NPS	PLGA	ESE	Q	Breast	MCF-7	TM	XM	Jain et al. (2013)
				Colon	Caco2
NPs	HA- PBCA-α-TPh-PEG-SC	RP	MH	Lung	A549	–	S180 XM	Abbad et al. (2015)
				Hepatic	L02
PC	PEG	CM	CUR	Glioma	C6	–	–	Dey et al. (2015)
PC	PEG	CM	CUR	Prostate	PC-3	–	–	Safavy et al. (2007)
PC	PEG	CM	CUR	Pancreas	MiaPaCa2, PANC-1, BxPC-3, AsPC-1	GM	–	Li et al. (2009)
PC	PEG	CM	RV	Cervice	HeLa	BT	–	Wang et al. (2016)
				Breast	MCF-7
PC	CMCT	CM	Q	Hepatic	HepG2	PTX	HepG2 XM	Wang et al. (2014)
PC	PEG	CM	CUR	Cervice, Breast	HeLa, EMT6	–	EMT6 XM	Lv et al. (2015)
PC	PEG-DTE	CM	CUR	Breast	MDA-MB-231	–	–	Shpaisman et al. (2012)
PC	PEG	CM	CA	Breast	MDA-MB-231	BZ	–	Su et al. (2011)
PC	HA-PEI	CM	EGCG	Colon	HCT-116	GB	–	Liang et al. (2016)
PC	Dex	FRG	CA	Pancreas	MiaPaca-2, PL45	–	–	Vittorio et al. (2012)
PC	Dex	FRG	CA	Neuroblastoma	IMR-32, IMR-32-CisRes, BE(2)-C	–	XM	Vittorio et al. (2016a)
PC	Dex	ELC	CA	Neuroblastoma	IMR-32	–	–	Vittorio et al. (2016b)
PC	GL	FRG	GA	Prostate	DU-145, PC-3	–	–	Cirillo et al. (2010)
				Kidney	A498
PC	PMAA	FRG	Q	Cervice	HeLa	–	–	Puoci et al. (2012)
MCs	GL-Dex	SA-GP-CK	PPs	Breast cancer	MCF-7	–	–	Zhou et al. (2012)
PMs	PVP-PEG	EE	PPs	Glioblastoma	DBTRG-05MG	–	–	Wang et al. (2015a)
MCs	GL-Dex	SA-GP-CK	CUR	Cervice	HeLa	–	HM	Zhang et al. (2014a)
PMs	KT	SE	CUR	Cervice	HeLa	–	–	Curcio et al. (2015a)
PMs	GL	Se	CUR	Lung	H1299	–	–	Curcio et al. (2015b)
MCs	CS	SA	CUR	Cervice	HeLa	–	–	Sahu et al. (2008b)
MCs	ZN-PEG	SA	CUR	Ovarian	NCI	–	HM	Podaralla et al. (2012)
MCs	CT-STA	SA	CUR	Colon	Primary	–	XM	Wang et al. (2012b)
MCs	PEG-PAE	SE	CUR	Cervice	HeLa	–	–	Lv et al. (2013)
MCs	PEG-PLA	SE	CUR	Breast	MCF-7	DOX	XM	Lv et al. (2016)
MCs	PEG-PCL	TLE	CUR	Ovarian	A2780t	–	–	Gou et al. (2015)
MCs	PEG-PCL	TLE	CUR	Breast	MDA-MB-436	–	–	Zhu et al. (2015)
MCs	PEG-PCL	SA	CUR	Breast	4T1	–	4T1 XM	Liu et al. (2013)
MCs	PEG-PCL	TLE	CUR	Cervice	HeLa	–	XM	Mikhail et al. (2014)
				Colon	HT-29
MCs	PEG-PCL	TLE	CUR	Lung	LL/2	DOX	XM	Wang et al. (2013)
MCs	PEG-PCL	SA	CUR	Lung	LL/2	–	ZF	Gong et al. (2013)
MCs	LNA-PEG-PCL	SA	CUR	Cervice	HeLa	–	HM	Song et al. (2014)
				Lung	A549
MCs	PEG -PAC	SA	CUR	Cervice	HeLa	–	–	Sahu et al. (2008a)
PMs	PEG-OA	TLE	CUR	Brain	U87MG	–	–	Erfani-Moghadam et al. (2014)
MCs	PEG2000-DSPE	TLE	CUR	Ovarian	SK-OV-3TR	PTX	–	Abouzeid et al. (2014)
MCs	PEG2000-DSPE	TLE	CUR	Ovarian	NCI	PTX	SK-OV-3TR XM	Sarisozen et al. (2014)
MCs	PEG2000-DSPE	TLE	CUR	Colon	HCT-116	DOX	XM	Abouzeid et al. (2013)
MCs	PEG-DOX	SA	CUR	Cervice	HeLa	DOX	HepG2 XM	Zhang et al. (2016)
				Hepatic	HepG2
MCs	PX-PEG-SC	SE	CUR	Ovarian	NCI	–	–	Saxena & Hussain (2013)
MCs	PX F127 F68	TLE	CUR	Cervice	HeLa	–	–	Sahu et al. (2011)
MCs	PX F127	TLE	RV, CUR	Ovarian	SKOV-3	DOX	HM	Carlson et al. (2014)
MCs	PX F127	TLE	RV, Q	Ovarian	SKOV-3	DOX	HM	Cote et al. (2015)
MCs	PCL-PEG-SC	TLE	RV	Breast	MCF-7	–	–	Wang et al. (2015b)
MCs	AP-E3	rDNA	RV	Glioblastoma	A-172	–	–	Kim et al. (2015a)
MCs	PLA-PEG	TLE	EGCG	Pancreas	MiaPaca-2	–	–	Sun et al. (2014a)
MCs	CS	SA	EGCG	Colon	HT-29	–	–	Haratifar et al. (2014b)
MCs	CS	SA	EGCG	Colon	–	–	XM	Haratifar et al. (2014a)
CNs	GO	RM	TPs	Colon	HT29, SW48	–	–	Abdolahad et al. (2013)
CNs	GO	RM	RV	Ovarian	A2780	–	–	Gurunathan et al. (2015)
CNHs	PCL-MWNT	ESP	TPs	Lung	A549	–	–	Shao et al. (2011)
				Hepatic	HepG2
CNHs	GL-MWNT	CG	CA	Prostate	DY-145, PC-3, LNCap	RT	–	Castro Nava et al. (2016)
CNHs	GL-MWNT	CG	CA	Cervice	HeLa	–	–	Cirillo et al. (2013b)
CNHs	PMAA-MWNT	RC	Q	Cervice	HeLa	–	–	Cirillo et al. (2013a)
CNHs	PMAA-MWNT	RC	Q	Neuroblastoma	IMR-32	CP	–	Vittorio et al. (2014a)
MNPs	Fe-CA	CPM	CUR	Breast	MCF-7	–	–	Wani et al. (2011)
MNPs	HA-Fe	LbL	CUR	Colon	Caco-2	–	–	Manju & Sreenivasan (2011)
	PVP-Fe			Glioma	C6
MNPs	Fe-PX F127	NPR	CUR	Pancreas	HPAF-II, Panc-1	–	XM	Yallapu et al. (2013)
MNPs	Fe-DEX	SM	CA	Pancreas	MIA Paca2	–	–	Vittorio et al. (2014b)
MNPs	Fe	KL	EGCG	Colon	CT-26	–	XM	Xiao et al. (2015)
MNPs	Ni	ED	Q	Hepatic	SMMC-7721	–	–	Guo et al. (2009)

PEG2000-DSPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 5-FU, 5-fluorouracil; AA, acrylic acid; ALG, alginate; AP, apolipoprotein; BT, bicalutamide; BZ, bortezomib; BSA, bovine serum albumin; CPM, capping method; CNHs, carbon nanohybrids; CNs, carbon nanostructures; CMCT, carboxymethyl chitosan; CS, casein; CA, catechin; CL, cellulose; KM, chelation method; CHT, chitin; CT, chitosan; CP, cisplatin; CG, coating; CM, condensation method; CK, crosslinking; CUR, curcumin; DTE, desaminotyrosyl-tyrosine ethyl ester; Dex, dextran; DOX, doxorubicin; EAC, Ehrlich ascites carcinoma; ED, electrochemical deposition; ESP, electrospinning; EFS, electrostatic field system; ESE, elmusion solvent evaporation; EE, emulsion evaporation; EM, emulsion method; EP, emulsion polymerization; ELC, enzyme laccase catalysis; EGCG, epigallocatechin gallate; EU, eudragit; FB, fibrinogen; FA, folic acid; FRG, free radical grafting; GA, gallic acid; GL, gelatin; GM, gemcitabine; GP, genipin; GB, granzyme B; GO, graphene oxide; GG, guar gum; HM, healthy mice; HSA, human serum albumin; HA, hyaluronic acid; HYs, hydrogels; IG, ionic gelation; KT, keratin; LbL, layer-by-layer; LNA, linoleic acid; MNPs, magnetic nanoparticles; MI, maleimide; MCs, micelles; MH, morin hydrate; MWNT, multi-walled carbon nanotubes; NFs, nanofibers; NPs, nanoparticles; NPR, nanoprecipitation; NIPAA, N-isopropylacrylamide; VP, N-vinyl-2-pyrrolidone; OA, oleic acid; PTX, paclitaxel; PAC, palmitic acid; pp, phosphopeptide; PPs, plant polyphenols; PX, poloxamers; PAGA, poly(acrylamidoglycolic acid); PA, poly(acrylates); PAE, poly(anhydride esters); PBCA, poly(butyl cyanoacrylate); PCL, poly(caprolactone); PCA, poly(cyanoacrylates); PEC, polyelectrolyte; PEG-mA, poly(ethylene glycol) acrylate; PEG-DA, poly(ethylene glycol) diacrylate; PEG, poly(ethylene glycols); PEI, poly(ethyleneimine); PLA, poly(lactic acid); PLGA, poly(lactide-co-glycolide) acid; PMAA, poly(methacrylic acid) ; PVP, poly(vinyl pyrrolidone); PC, polymer conjugate; PMs, polymersomes; PmPs, pomgranade polyphenols; Q, quercetin; RC, radical coupling; RP, radical polymerization; RT, radiotherapy; rDNA, recombinant DNA; RM, reduction method; RV, resveratrol; ROP, ring opening polymerization; SA, self-assembly; SM, solvation method; SE, solvent evaporation; STA, stearic acid; SC, succinate; TM, tamoxifen; TPs, tea polyphenols; TF, theaflavin; TLE, thin layer evaporation; TPh, tocopheryl; XM, xenograft mice; ZF, zebrafish; ZN, Zein.

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