Polymeric nanoparticles for targeted treatment in oncology: current insights

Figures & data

Figure 1 Schematic illustration of polymeric nanoparticle platforms.

Note: Blue color represents the polymeric platform.

Figure 2 Overview of targeting approaches of polymeric nanoparticles in cancer.

Table 1 Polymeric nanoparticles developed for passive delivery of drugs to treat various cancers

Polymer	Drug	Cancer cell line	In vitro and in vivo study	Reference
PLGA	PTX	Human cervical carcinoma cells (HeLa)	In vitro and in vivo	^Citation51
	Cisplatin	Colon adenocarcinoma cells	In vitro and in vivo in mice	^Citation52,Citation53
	5-FU	Glioma (U87MG) and breast adenocarcinoma (MCF-7) cell lines	In vitro	^Citation54
	DOX	MDA-MB-231 breast cancer cells	In vitro	^Citation55
		HeLa cells	In vitro	^Citation56
		Fibroblast cells	In vitro	^Citation57
	TMX	Breast cancer (C1271) cells	In vivo in mouse	^Citation58
		MCF-7 cells	In vivo in mouse	^Citation59
	Gemcitabine	Pancreatic cancer cells (PANC1)	In vitro	^Citation60
PLGA–mPEG	Cisplatin	Prostate cancer (LNCaP) cells	In vitro	^Citation61
PLGA–mPEG + CMC		Ovarian cancer (IGROV1-CP) cells	In vitro and in vivo in mice	^Citation62
GCS	5-FU	Hepatocellular carcinoma (HCC)/SMMC-7721 cells	In vitro and in vivo in mouse	^Citation63,Citation64
HA–PEG–PLGA		EAT cell lines	In vitro and in vivo in mice	^Citation65
PBLG–PEG		Human colon cancer (LoVo) cell lines and squamous carcinoma (Tca 8113) cell	In vitro and in vivo in mice	^Citation66
mPEG-b-P(CL-co-HCL)	DOX	HepG2 cells	In vitro	^Citation67
l-PLGA–HSA		Rat glioblastoma	In vivo in rat	^Citation68
PLC and PDLLA	TMX	HeLa and MCF-7 cells	In vitro	^Citation69
PAMAM–cholesterol		MCF-7 cells	In vitro	^Citation70
PEO–PCL	PTX and TMX	Ovarian adenocarcinoma (SKOV3) and MDR-1-positive (SKOV3TR) cells	In vitro and in vivo in nude mice	^Citation71
PEG–PDLLA	Gemcitabine	Human pancreatic cancer (SW1990) cells	In vitro	^Citation72
Poly(butyl cyanoacrylate)	Epirubicin	Human carcinoma (HeLa and A549) cell lines	In vitro	^Citation73

Abbreviations: PLGA, poly(lactide-co-glycolide); PTX, paclitaxel; 5-FU, 5-fluorouracil; DOX, doxorubicin; TMX, tamoxifen; mPEG, methoxy-polyethylene glycol; CMC, carboxymethyl cellulose; GCS, glycosylated chitosan; HA, hyaluronic acid; PEG, polyethylene glycol; EAT, Ehrlich ascites tumor; PBLG, poly(γ-benzyl-l-glutamate); P(CL-co-HCL), poly(ε-caprolactone-co-γ-hydroxyl-ε-caprolactone); HSA, human serum albumin; PLC, poly(d,l-lactide-co-caprolactone); PDLLA, poly(d,l-lactide); PAMAM, polyamidoamine; PEO, polyethylene oxide; PCL, polycaprolactone.

Table 2 Polymeric nanoparticles employed for ligand-based delivery of drugs to treat various cancers

Polymer	Drug	Targeting ligand	Cellular target	Cancer cell line	In vitro and in vivo study	Reference
PLGA	DOX	Cyclo-(1,12)-PenITDGEATDGC (cLABL)	ICAM-1	Lung epithelial cancer cells (A549)	In vitro	^Citation74
	Gemcitabine	Anti-EGFR monoclonal antibody	EGFR	Pancreatic cancer cells	In vitro	^Citation75
PLGA-b-PEG	Docetaxel	A10 aptamer	PSMA	Prostate cancer (LNCaP) cells	In vivo in nude mice	^Citation76
	Docetaxel	A10 2′-fluoropyridine RNA aptamer	PSMA	LNCaP cells	In vitro and in vivo in mice	^Citation77
	^14C-paclitaxel	A10 aptamer	PSMA	LNCaP cells	In vitro and in vivo in mice	^Citation76
	Pt (IV) prodrug	A10 aptamer	PSMA	LNCaP cells	In vitro and in vivo in mice and rats	^Citation78,Citation79
	Cisplatin	Cyclic Arg-Gly-Asp (cRGD) peptide	αvβ3 integrin	Breast (MCF-7) and prostate cancer (PC3 and DU145) cells	In vitro and in vivo in nude mice	^Citation80
PLGA–PEG	DOX	Novel peptide	EGFR	Human ovarian cancer (SKOV3) cells	In vitro and in vivo in mice	^Citation81
mPEG	Mitomycin C	FA	Folate receptor	HeLa cells	In vivo in mice	^Citation82
Pullulan acetate	Epirubicin	FA	Folate receptor	Nasopharyngeal epidermal carcinoma (KB) cell lines	In vitro	^Citation83

Abbreviations: PLGA, poly(lactide-co-glycolide); DOX, doxorubicin; ICAM-1, intercellular adhesion molecule-1; EGFR, epidermal growth factor receptor; PSMA, prostate-specific membrane antigen; PEG, polyethylene glycol; mPEG, methoxy-polyethylene glycol; FA, folic acid.

Table 3 Clinically approved polymeric nanomedicine for oncologic treatment

Polymeric platform	Product description	Therapeutic agent	Commercial name	Indication	Administration
Polymer–protein conjugate	SMANCS	Neocarzinostatin	Zinostatin Stimalmer	Hepatocellular carcinoma	Intra-arterial
	PEG–l-asparaginase	Asparaginase	Oncaspar	Acute lymphoblastic leukemia	Intravenous, intramuscular
	PEG–GCSF	GCSF	Neulasta/PEG filgrastim	Prevention of neutropenia associated with cancer chemotherapy	Subcutaneous
Polymeric micelle	Methoxy-PEG–poly (d,l-lactide)–paclitaxel micelle	Paclitaxel	Genexol-PM	Metastatic breast cancer	Intravenous

Abbreviations: SMANCS, styrene–maleic anhydride–neocarzinostatin; PEG, polyethylene glycol; GCSF, granulocyte colony-stimulating factor.

Table 4 Polymeric nanoparticle-based therapeutics undergoing clinical investigation

Polymeric platform	Description	Product name	Indication	Status
Polymer–protein conjugate	PEG–IFNα 2a	PEG-asys	Melanoma, chronic myeloid leukemia, and renal cell carcinoma	Phase I/II
	PEG–IFNα 2b	PEG-Intron	Melanoma, multiple myeloma, and renal cell carcinoma	Phase I/II
	PEG–arginine deaminase	ADI-PEG20	Hepatocellular carcinoma	Phase I
	PEG–glutaminase combined with a glutamine anti-metabolite DON	PEG–PGA and DON	Various cancers	Phase I/II
Polymer–drug conjugate	Polyglutamate–paclitaxel	CT-2103; Xyotax	Various cancers, particularly non-small-cell lung cancer; ovarian cancer as a single agent or in combination therapy	Phase III
	Polyglutamate–camptothecin	CT-2106	Colorectal and ovarian cancer	Phase I/II
	HPMA copolymer–doxorubicin	PK1; FCE28068	Various cancers, particularly lung and breast cancer	Phase II
	HPMA copolymer–doxorubicin–galactosamine	PK2; FCE28069	Hepatocellular carcinoma	Phase I/II
	HPMA copolymer–paclitaxel	PNU166945	Various cancers	Phase I
	HPMA copolymer–camptothecin	MAG-CPT	Various cancers	Phase I
	HPMA copolymer–carboplatin platinate	AP5280	Various cancers	Phase I/II
	HPMA copolymer–DACH-platinate	AP5346; ProLindac	Ovarian cancer	Phase II
	Dextran–doxorubicin	AD-70, DOX-OXD	Various cancers	Phase I
	Modified dextran–camptothecin	DE-310	Various cancers	Phase I
	PEG–camptothecin	Prothecan	Various cancers	Phase II
	PEG–irinotecan	NKTR-102	Ovarian, breast, and colorectal cancer	Phase II/III
	Poly(iso-hexyl-cyanoacrylate)–doxorubicin	Transdrug	Hepatocellular carcinoma	Phase I/II
	Polycyclodextrin–camptothecin	IT-101	Metastatic solid tumors	Phase I
Polymeric micelle	PEG–polyglutamate micelle with SN-38	NK012	Breast cancer	Phase II
	PEG–polyaspartate micelle with paclitaxel	NK105	Advanced stomach cancer	Phase II
	Pluronic L61 and F127 micelle with doxorubicin	SP1049C	Adenocarcinoma of esophagus, gastroesophageal junction, and stomach	Phase III
	PEG–poly(d,l-lactide) micelle with paclitaxel	Genexol-PM	Non-small-cell lung, pancreatic, bladder, and ovarian cancer	Phase II
	PEG–poly(γ-benzyl-l-glutamate) micelle with cisplatin	NC-6004	Solid tumors	Phase I/II
	PEG–polyaspartate micelle with doxorubicin	NK-911	Various cancers	Phase II
	Cyclodextrin–PEG micelle with camptothecin	CRLX101	Lung and ovarian cancer	Phase II

Abbreviations: PEG, polyethylene glycol; IFN, interferon; DON, 6-diazo-5-oxo-l-norleucine; PGA, polyglutamic acid; HPMA, hydroxypropylmethacrylamide; DACH, diaminocyclohexane; SN-38, 7-ethyl-10-hydroxy-camptothecin.

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