Journal of Drug Delivery

Review Article

Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

Table 1

Impact of functionalized CNTs on cancer cell lines.


Cancer type	CNT properties		Bioactive molecule	Objective	Cell line	Repercussion of the study	Reference
Cancer type	Type	Functionalization	Bioactive molecule	Objective	Cell line	Repercussion of the study	Reference

Brain cancer	MWCNTs	—	—	Influence of purity and surface oxidation on cytotoxicity of MWCNTs with human neuroblastoma cells	Human neuroblastoma cell line SH-SY5Y	With prolonged cultures, loss of cell viability was minimal for preparations with 99% purity, but significant adverse effects were detected with 97% purity and with acid treated preparations. A concentration of 5–10 g/mL of MWCNTs seems ideal for gene and drug therapy against cancer	[115]
	SWCNTs	Phospholipid-polyethylene glycol (PEG), protein A, fluorescein labeled integrin mAb	—	Functional SWCNTs based on an integrin mAb for the highly efficient cancer line	Human U-87MG glioblastoma cell, MCF-7	In vitro study revealed that SWCNT-PEG-mAb presented a high targeting efficiency on integrin -positive U87MG cells with low cellular toxicity.	[116]
	MWCNTs	Angiopep-2, PEGylated	Doxorubicin	Targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized MWCNTs modified with angiopep-2.	C6 glioma cells	Angiopep-2 modified PEGylated MWCNTs showed better antiglioma activity, good compatibility, and low toxicity.	[117]
	MWCNTs	Poly(acrylic acid) and folic acid	Doxorubicin	Dual targeted delivery of doxorubicin to cancer cells using folate conjugated magnetic MWCNTs.	U87 human glioblastoma cells	Dual targeting of doxorubicin from magnetic MWCNTs showed enhanced cytotoxicity toward U87 human glioblastoma cells compared with free doxorubicin.	[118]
	SWCNTs	CD133 monoclonal antibody (mAB)	—	Photothermolysis of glioblastoma stem like cells targeted by CNT conjugated with CD133 mAB.	GBM-CD133⁺ and GBM-CD133⁻ cells	GBM-CD133⁺cells were selectively targeted and eradicated whereas CD133⁻ cells remained viable after incubation with SWCNT-CD133mAB. GBM-CD133⁺cells pretreated with SWCNT-CD133mAB and irradiated by near-infrared laser for 2 days did not exhibit sustainability of cancer stem like cells features for tumor growth.	[119]
	MWCNTs	—	SiRNA and DNA	Internalization of MWCNTs by microglia: possible application in immunotherapy of brain tumors.	BV2 microglia and GL261 glioma cells	Uptake of MWCNTs by both BV2 and GL261 cells in vitro without any significant signs of cytotoxicity.	[120]

Blood cancer	SWCNTs	Sgc8c aptamer	Daunorubicin (Dau)	Reversible targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped CNTs	Human T cell leukemia cell MOLT-4 and U266 myeloma cells	The tertiary complex Dau-aptamer-SWCNTs was internalized effectively to MOLT-4 cells but not to U266 cells and is less toxic in U266 as compared to Dau-aptamer-SWCNTs complex is able to selectively target MOLT-4 cells	[121]

Breast cancer	SWCNTs	Polyethylene glycol (PEG) and Poly (maleic anhydride-alt-1-octadecene) (PMHC₁₈)	—	Optimization of surface chemistry on single walled CNTs for in vivo photothermal ablation of tumors	Balb/c mice bearing 4T1 tumors	PEG-PMHC₁₈-SWCNTs showed ultralong blood circulation half-lives though showing high uptake in the tumor tend to accumulate in the skin dermis	[122]
	MWCNTs	Polyamidoamine dendrimer(d)	FITC-labelled antisense c-myc oligonucleotides (asODN)	Synthesis and characterization of polyamidoamine dendrimer coated MWCNTs and their application in gene delivery systems	MCF-7 and MDA-MB-435 human breast cancer cell line, liver cancer cell HepG2	Laser confocal microscopy confirmed the entry of asODN into the tumor cell, within 15 min of incubation. asODN-dMNTs composites inhibit the cell growth and downregulated the expression of the c-myc gene and C-Myc protein.	[123]
	SWCNTs	Insulin-like growth factor 1 receptor (IGF 1R-) specific and nonspecific monoclonal antibodies (mABs)	—	Bioconjugated CNTs for targeting cancer biomarkers	BT-474 and MCF-7 breast cancer cells	mAB-CNT as field effect transistors are very promising biosensor candidates to detect cancer cells.	[124]
	SWCNTs	Distearoylphosphatidy-lethanolamine (DSPE)-PEG-Amine, mouse double minute 2 homolog (MDM2)	SiRNA	Functionalized SWCNTs enables efficient intracellular delivery of SiRNA targeting MDM2 to inhibit breast cancer cells growth	B-Cap-37 breast carcinoma cells	f-SWCNTs showed significant efficiency in carrying SiRNA and SiRNA-MDM2 complexes in B-Cap-37 cells and caused inhibition of proliferating cells.	[125]
	SWCNTs	—	—	SWCNT nanobomb agents for killing breast cancer cells.	Human BT-474 breast cancer cells	SWCNT-based systems were capable of killing cancer cells without causing toxicity to the surrounding cells.	[126]
	SWCNTs	Polyethylene glycol	Paclitaxel (PTX)	Drug delivery with CNTs for in vivo cancer treatment	4T1 murine breast cancer cell line	SWCNT-PTX affords higher efficacy in suppressing tumor growth without causing obvious toxic effects to normal organs.	[110]
	SWCNTs	anti-HER2 chicken IgY antibody	—	Anti-HER2 IgY antibody-functionalized SWCNTs for detection and selective destruction of breast cancer cells	HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells	Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. HER2 IgY-SWCNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells.	[78]

Colon cancer	MWCNTs	—	—	Vertically aligned MWCNTs to preferentially entrap highly metastatic cancer cells	SW-48 cells and HT-29 human colon adenocarcinoma cell	Vertically aligned MWCNT entrap higher metastatic cancer in larger fraction than lower metastatic grades. Cell rigidity due to fixation decreases the entrapment efficiency	[127]

Colon cancer	SWCNTs	Bovine serum albumin-antibody, fluorescein	Doxorubicin	Triple functionalization of SWCNTs with doxorubicin, a monoclonal antibody and a fluorescent marker for targeted cancer therapy	WiDr Human colon adenocarcinoma cells	The triple fictionalized complex was efficiently taken by cancer cells with subsequent intracellular release of doxorubicin.	[128]

Liver cancer	MWCNTs	Polyamidoamine dendrimer(d)	FITC-labelled antisense c-myc oligonucleotides (asODN)	Synthesis and characterization of polyamidoamine dendrimer coated MWCNTs and their application in gene delivery systems	HEP-G2 human hepatoma cells	Laser confocal microscopy confirmed the entry of asODN into the tumor cell, within 15 min of incubation. asODN-dMNTs composites inhibit the cell growth and downregulated the expression of the c-myc gene and C-Myc protein.	[123]
Liver cancer	SWCNTs	Chitosan and folic acid	Doxorubicin	Targeted DDS based on chitosan and folic acid modified SWCNTs for controllable loading/release of anticancer agent doxorubicin.	Hepatocellular carcinoma SMMC-7721 cell lines	The chitosan-folic acid modified SWCNTs not only kill cancer cells efficiently, but also display much less in vivo toxicity than free doxorubicin.	[129]

Lymph node Metastatis	MWCNTs	Magnetic	Gemcitabine (GEM)	Magnetic functionalized CNTs as drug vehicles for cancer lymph node metastasis treatment	BxPC-3 pancreatic cancer cells	mMWCNTs-GEM had high antitumor activity resulting in successful regression and inhibition of lymph node metastasis under the magnetic field.	[130]

Kidney cancer	SWCNTs	—	—	Effect of SWCNTs on human HEK293 cells	Human kidney embryo cell HEK-293 cells	SWCNTs inhibit HEK293 cell proliferation and decrease cell adhesive ability in a dose and time dependent manner.	[131]
Kidney cancer	SWCNTs	Phenosafranine (PS) and Nile blue (NB) dyes	—	SWCNTs modified with organic dyes: synthesis, characterization, and potential cytotoxic effects	Baby hamster kidney fibroblast cells BHK-21 cell line	Cytotoxicity of dye modified SWCNT displayed low toxicity in the dark while being higher in the dark and higher in the presence of light	[132]

Cervical cancer	SWCNTs	chitosan and folic acid, FITC	—	Functional SWCNTs chitosan conjugate for tumor cell targeting	Human cervical carcinoma HeLa cells	Conjugates provide new options for targeted drug delivery and tumor cell sensing because of the combined intrinsic properties of CNTs and the versatility of chitosan	[133]
Cervical cancer	MWCNTs	Folate and iron	Doxorubicin	Folate and iron defunctionalized MWCNTs as dual targeted drug nanocarrier to cancer cells.	HeLa cells	This dual targeted nanocarrier has efficient biological and magnetical targeting capabilities towards HeLa cells and considered safe for biological applications.	[134]

Cervical cancer	SWCNT, MWCNT	Acid-treated SWCNTs, acid-treated MWCNTs, amylose wrapped SWCNTs.	—	The influence of CNT scaffolds on human cervical carcinoma HeLa cells viability and focal adhesion kinase expression.	HeLa cells	Cells cultured on SWCNTs and on acid-treated SWCNTs were found to undergo apoptosis. The cells cultured on MWCNTs, acid-treated MWCNTs, and amylose wrapped SWCNTs were found to be viable. This may be due to focal adhesion kinases (FAK) expression which is responsible for controlling the cell viability	[135]
Cervical cancer	SWCNTs	Polysaccharides [sodium alginate (ALG) and chitosan (CH)]	Doxorubicin (DOX)	Targeted delivery and controlled release by doxorubicin to cancer cells using modified CNTs.	HeLa cells	The DOX released from the modified nanotubes has been shown to damage nuclear DNA and inhibit the cell proliferation.	[136]

Prostate cancer	SWCNTs	Polyethylenimine (PEI), Asn-Gly-Arg (NGR) peptide	SiRNA	Synergistic anticancer effect of RNAi and photothermal therapy mediated by functionalized SWCNTs.	Human prostate carcinoma (GIV) cell PC-3 cells	SWCNT-PEI-SiRNA-NGR induces severe apoptosis and suppresses the proliferating of PC-3 cells without any level of toxicity	[137]