Nanomaterials as nanocarriers: a critical assessment why these are multi-chore vanquisher in breast cancer treatment

Figures & data

Figure 1. Morphology and medical illustration of the various types of breast cancer.

Table 1. Different types of breast cancer along with site of development and characteristics.

Type	Sub types	Sites of occurrence	Metastasis	Diagnosis	Treatment	References
Pre-invasive (Breast Cancer)	IDC	Ducts that carry milk to nipple	Yes	Early stage is possible	Local: surgery/radiation systemic: chemical/hormonal, therapies	[12]
	ILC	Milk glands (lobules)	Yes	Difficult to detect than IDC	Local: surgery/ radiation Systemic: chemical/hormonal, therapies	[12]
Invasive	EBC	Arises in the breast	May or may not	Detection is difficult in metastatic areas	Local: surgery/radiation and adjuvant systemic therapy	[13]
	LABC	In breast and is larger than 5cm	Yes	advanced breast cancer test	Combination of chemotherapy, surgery, radiotherapy, targeted and hormonal therapies.	[14]
	MBC	Arises in the breast	Yes	Difficult to diagnose	Chemotherapy, hormone therapy	[5]
	HRP	Breast	Yes	Immunohistochemical staining assay, or Immunohistochemistry (IHC).	Chemotherapy with targeted hormonal therapies	[15]
	HER2 P	Breast	Yes	IHC, FISH, SPoT-Light HER2 CISH and Inform HER2 Dual ISH test	Trastuzumab (Herceptin™) or lapatinib (Tykerb™), targeted therapy along with chemotherapy are in use.	[16]
	TN	Breast	Yes	mammograms, ultrasound, MRI, CAT scans, PET scans etc.	Surgery, radiation and chemotherapy.	[12]
Sarcomas and lymphomas	N.A	Muscle, fat or connective tissue	Yes	mammograms, MRI, CAT scans, ultrasound, PET scans etc.	Chemotherapy, radiotherapy and possibly surgery.	[17]
Paget’s Disease	N.A	Nipple and areola	Yes	Physical examination, mammogram, MRI, Ultrasound, Biopsy	Surgery, Mastectomy, radiation chemotherapy, hormone therapy.	[12]
Inflammatory	N.A	Breast or localized	Yes	Histologically	chemotherapy, surgery, radiation and possibly targeted therapy	[18]
Medullary	N.A	Breast ducts	Yes	Histologically	Surgery followed by chemotherapy	[12]
Mucinous	N.A	Milk duct	Less likely to spread	Physical examination, mammogram, MRI, Ultrasound, Biopsy	Lumpectomy, mastectomy, radiation, hormonal and chemotherapy.	[19]
Tubular	N.A	Breast's milk duct	Yes	Physical examination, mammogram, MRI, Ultrasound, Biopsy	Surgery followed by chemotherapy, surgery, radiation	[19]
Metaplastic (MBC)	N.A	Breast	Yes	Mammogram, Biopsy, ultrasound, FNA	Surgery followed by chemotherapy, surgery, radiation	[5]
Papillary breast cancer	N.A	Breast	Yes	Mammogram, biopsy, ultrasound, FNA	Surgery followed by chemotherapy, surgery, radiation	[20]

IDC: Invasive ductal carcinoma; ILC: Invasive lobular carcinoma; EBC: Early Breast Cancer; LABC: locally advanced breast cancer; MBC: Metastatic Breast Cancer; HRP: Hormone receptor positive; HER2 P: HER2 positive; TN: triple negative; IHC: immunohistochemistry; FISH: fluorescence in situ hybridization; SPoT-Light HER2 CISH: Subtraction probe technology chromogenic in situ hybridization; Inform HER2 Dual ISH test: inform dual in situ hybridization; FNA: fine needle aspiration.

Figure 2. Overview of targeted drug delivery.

Figure 3. Passive and active drug delivery carried out by various methods.

Figure 4. Frequently used organic and inorganic nanocarriers in breast cancer.

Table 2. Nanotechnology based FDA approved products against breast cancer.

Nano carrier	Active agent	Drug	Mode of action	Company	Admin.route
Liposomes	Doxorubicin	Doxil/ Caelyx	Produces EPR effect through passive targeting.	Orthobiotech, Schering-Plough	Intravenous [IV]
	Doxorubicin	Myocet	Targeted MPS; carry slow drug release into blood similar to prolonged infusion	Elan Pharmaceuticals/Sopherion Therapeutics	IV
	Doxorubicin	Lipodox	Penetrate the cells, binds with chromatin &hindered DNA synthesis.	Sun Pharma	IV
	Paclitaxel	Taxol^®	Microtubule-stabilizing drug. Block cell in the G2/M phase of cell cycle.	Bristol-Myers Squibb Co.	IV
Micelles	Paclitaxel	Genexol-PM Cynviloq IG-001	Drug binds specifically to the beta- tubuline and then enhances the polymerization of tubuline to stable microtubules.	Samyang	IV
Protein Nps	Paclitaxel	Abraxane	Produces EPR effect through passive targeting.	Abraxis Bioscience, Astrazeneca	IV
	Trastuzumab emtansine	Kadcyla	Trastuzumab inhibit cancer growth by binding withHER2/neu receptor while mertansine on entering on cells and kill them by binding to tubulin.	Roche and ImmunoGen	IV
NP delivery	Paclitaxel	Nanoxel	Act as an anti-microtubule. Prevent growth and spread of cancer cells.	Dabur Pharma	IV

Table 3. Nanotechnology based products in clinical trials against breast cancer.

Nano carrier	Active agent	Drug	Mode of action	Current Status	Company	Admin. route	References
Liposomes	Paclitaxel	LEP-ETU	Hinder or block cell cycle and destroy cancerous cells	Phase II	Neopharma	IV	[232]
	Taxotere	LE-DT [Docetaxel]	Anti-microtubule agent, prevents cell division by promoting the assembly and stabilization of microtubules	Phase I	Neo-Pharm. Inc. [NEOL]	IV	[233]
	Cisplatin	Lipoplatin	Not known	Phase III	Regulon	IV	[234]
	Irinotecan [PEGylated]	MM-398	Irinotecan linked reversibly with topoisomerase 1-DNA & inhibit re-ligation of the single-strand breaks, result in cell death via damage of ds DNA	Phase III	Nektar Therapeutics	IV	[235]
	Paclitaxel	EndoTAG-I	Targets the vascular endothelial cells and lead to cell damage and death	Phase II	Medigene/SynCore Biotechnology	IV	[236]
	Mitoxantrone	[LEM-ETU]	Stop nucleic acid synthesis &intercalates with DNA in vitro, exact mechanism of action is under research	Phase II	Taj Pharmaceuticals Ltd.	IV	[237]
	Doxorubicin	Thermodox®	Temperature-triggered doxorubicin release	Phase III	Celsion	IV	[238]
	Doxorubicin	MM-302 HER2-targeted liposomal	Binds specifically to tumour cells [overexpress HER2] and undergoes receptor-mediated endocytosis, releasing doxorubicin inside the cell.	Phase II	Merrimack Pharmaceuticals	IV	[239]
	Vinorelbine	Vinorelbine [INX-0125]	Mitosis inhibitors; Tubulin polymerization inhibitors	Phase II	TLC	IV	[240]
Polymeric NPs	Paclitaxel	Genexol [PEG-poly[lactic acid]	Passive targeting via EPR effect	Phase 3	Samyang Biopharmaceuticals Corporation	IV Infusion	[241]
	Annamycin	Annamycin [Liposomeannamycin]	N. A	I/II		IV	[242]
	Doxorubicin, Paclitaxel, platinum baseddrugs, Docetaxel	Polymeric nanoparticles [50–200]	N. A	Phases III			[243]
	Oxaliplatin*	Oxaliplatin vectorized in chitosan NPs	pH dependent behaviour	Pre-clinical [In vitro studies]	DR Reddy's	IV	[244]
Micelles	Paclitaxel	NK105	N.A	Phase 3	Nippon Kayaku	IV	[245]
Gold NPs	rhTNF	CYT-6091	N.A	Phase II	Cytimmune	IV	[117]
		Silica-Gold Shell	Photothermal				[116]
Arsenic Trioxide	As2O3	Trisenox®	Exact mechanism is not known	Pilot phase II	University of Texas Medical Branch, Galveston	IV	[246]

rhTNF: Recombinant human tumour necrosis factor alpha.

Table 4. Nanotechnology based inorganic nanocarriers used in research against breast cancer.

Nanomaterials	Morphology	Modification	Drug loaded	Cell line	Response	References
Gold NPs	Nanostars	TAT cell-penetrating peptide	N.A	BT549	Killing of cancerous cell while not effecting normal cells	[112]
	Nanorods	AS1411 DNA aptamer	Doxorubicin	MCF-7	90% cells death was observed	[125]
	N.A	PEGylate	N.A	SK-BR-3	Cell death	[115]
	N.A	PEGylated	HER-2 antibody	SK-BR-3	Higher cytotoxic towards cancerous cells	[118]
	N.A	PEGylated	Trastuzumab	SK-BR-3	Breakage in double stranded DNA	[130]
MNPs	N.A	N.A	Trastuzumab targeted HER2	HER2 receptors	Radiological nanoprobes used to detect breast xenografts	[148]
MNPs	N.A	Oleic acid – Pluronic	Doxorubicin		Antiproliferative effect	[144]
TiO2 NPs	N.A	N.A	Doxorubicin	Tumour cells	Increased anticancer potential	[157]
Budotitane						[155]
Titanium salan						[156]
FePt@CoS2	Yolk-shell NPs	N.A	N.A	HeLa cells	IC50 = 35.5 ± 4.7 ng Pt/ml	[54]
Au-Fe3O4 NPs	Dumbbell	Herceptin antibody	Platinum based	[SK-BR-3]		[179]
Ni NPs	N.A	N.A	N.A	MCF7	ROS induced cytotoxicity	[200]
Cobalt NPs	N.A	N.A	Cobalt ferrites NPs	MCF7	Apoptosis	[200]
CuO NPs	N.A	N.A	N.A	MCF7	Apoptosis in breast cancer cells	[208]
AgNPs	N.A	N.A	N.A	MDA-MB-231	ROS and caspases-3 through activation of LDH	[214]
As2O3	N.A	N.A	N.A	MCF-7 and T47D	Inhibition of oestrogen receptor	[221]
As2O3	N.A	N.A	N.A	MCF7cells	Apoptosis via activation of caspase-3 and the reduction in expression of HERG	[222]
Bimetallic NPs [gold-silver]	N.A	S2.2 aptamer	N.A	MCF-7	97% cell death observed	[124]

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