The Applications of Carbon Nanotubes in the Diagnosis and Treatment of Lung Cancer: A Critical Review

Figures & data

Figure 1 Scheme of SWCNT originating from a graphene sheet, while MWCNT has several graphene sheets according to the size. Carbon atoms were placed next to each other in a honeycomb structure. Reprinted from International Communications in Heat and Mass Transfer, Vol 78, Yazid MNAWM, Sidik NAC, Mamat R, et al, A review of the impact of preparation on stability of carbon nanotube nanofluids, Pages No. 253–263, Copyright (2016), with permission from Elsevier.²⁰

Figure 2 Evaluation of the similarity of straight MWCNTs and asbestos, and the effect of straight, curved MWCNTs and asbestos on mesothelial cells. Indeed, curved nanotubes are less dangerous for the cell than a straight CNTs or asbestos, and could better play their carrier role.

Table 1 Summary of Toxic Effects Obtained from Studies by Year Order

Researchers	Year	Research	Toxic Effects	Citation
Muller et al	2005	MWCNTs on lungs of Sprague–Dawley rats	Inducing inflammation, pulmonary lesions, and fibrosis	^Citation38
Srivastava et al	2011	MWCNTs on human’s lung cancer cell line-A549/in vitro	Making oxidative stress and apoptosis	^Citation34
Pacurari et al	2011	MWCNTs on mice lungs	Inducing cancer, and changes in genes expression	^Citation50
Wang et al	2011	SWCNTs on mice lungs	Inducing cancer	^Citation57
Hong Liu	2012	MWCNTs on mice lungs	Producing multiple lesions	^Citation37
Morimoto et al	2012	MWCNTs on mice lungs	Inducing pulmonary inflammation, and small granulomatous lesion	^Citation40
Guo et al	2012	MWCNTs on mice lungs	Inducing cancer, and changes in genes expression	^Citation51
Yu et al	2013	MWCNTs on male C57BL/6 mice lungs	Producing tumor	^Citation52
Rittinghausen et al	2014	MWCNTs on rat lungs	Producing tumors and cancer	^Citation22
Sargent et al	2014	MWCNTs on B6C3F1 mice lung	Inducing cancer	^Citation46
Sanpui et al	2014	SWCNTs on small airway epithelial cells/in vitro	Increasing vulnerability to infections	^Citation55
Luanpitpong et al	2014	SWCNTs on mice lungs	Inducing tumor	^Citation58
Luanpitpong et al	2014	SWCNTs on human’s lung epithelial cells/in vitro	Inducing tumor	^Citation60
Dymacek et al	2015	MWCNTs on mice lungs	Inducing inflammation, and fibrosis	^Citation42
Chen et al	2015	SWCNTs on lungs line cells/in vitro	Inducing cancer, and changes in genes expression	^Citation59
Virupaxi et al	2015	SWCNTs on rat’s lung epithelial cells/in vitro	Decreasing antioxidant levels, and inducing cell death	^Citation62
Pongrakhananon et al	2015	SWCNTs on human’s lung epithelial cells/in vitro	Inducing cancer and making resistance to apoptosis	^Citation63
Shvedova et al	2015	SWCNTs on human’s lung line cells/in vitro	Inducing cancer	^Citation64
Snyder-Talkington et al	2016	MWCNTs on mice lungs	Inducing inflammation, and fibrosis	^Citation43
Snyder-Talkington et al	2016	MWCNTs on mice lungs	Inducing inflammation, fibrosis, and lung adenocarcinoma	^Citation44
Suzui et al	2016	MWCNTs on male rats lungs	Inducing malignant mesothelioma and lung tumors	^Citation48
Kasai et al	2016	MWCNTs on F344 rats lungs	Inducing lung carcinomas	^Citation49
He et al	2016	CNT on human’s lung line cells/in vitro	Inducing malignancies	^Citation65
Stueckle et al	2017	MWCNTs on human’s lung epithelial cells/in vitro	Producing lung tumorigenesis	^Citation32
Zhou et al	2017	MWCNTs on human’s lung cancer cell line/in vitro	Observing genotoxic and cytotoxicity	^Citation33
Vlaanderen et al	2017	Workers in contact with MWCNTs	No functional difference in the lungs	^Citation35
Rahman et al	2017	MWCNTs on mice lungs	Inducing fibrosis, cancer, chronic inflammation, changes in genes expression, and tissue irritation	^Citation45
Voronkova et al	2017	SWCNTs on mice lungs	Inducing cancer, and overexpression of SOX9	^Citation56
Wang et al	2017	SWCNTs on human’s lung epithelial cells/in vitro	Promoting tumor, and metastasis	^Citation61
Dymacek et al	2018	MWCNTs on mice lungs	Changing in gene expression, cell proliferation, survival, oxidative phosphorylation pathway, mitochondrial dysfunction, transcription, and producing fibrosis	^Citation29
Fukai et al	2018	MWCNTs on the murine lung resident cells (GDL 1) and immune cells (RAW 264.7)	Inducing mutation in GDL 1 and producing inflammatory cytokines from RAW 264.7	^Citation36
Nahle et al	2019	SWCNTs and MWCNTs on rat’s alveolar macrophage cell line	Inducing inflammation mainly by MWCNTs, while SWCNTs more relying on apoptosis and destroyed mitochondrial function	^Citation31
Gaté et al	2019	MWCNTs on the lungs of Sprague–Dawley rats	Observing DNA damage	^Citation39
Wang et al	2020	CNTs on the experimental animals	Inducing pleural lesions, pleural fibrosis, inflammation, lung tumors, and virulent mesothelioma	^Citation26
Aoki et al	2020	MWCNT on the lungs of mice	No cancerous effect	^Citation53
Önera et al	2020	MWCNT on human’s bronchial cells/in vitro	Inducing methylation changes in CpG sites, and promoters of genes	^Citation47

Figure 3 Summary of diagnostic cases based on the changes in polar components. Targeted CNT sensors could be connected to a variety of modified vapors. In this way, with the help of this method screening make non-invasive diagnosis possible.

Table 2 Review of Studies and Results of Nano-Drug Delivery by CNT in the Treatment of Lung Cancer (by Year Order)

Researchers	Year	Type of CNTs	Functionalized with	Type of Drugs/Protein	Targeting	Results	Citations
Podesta et al	2009	MWCNT	Cation	siRNA	A549 in vivo	Results were desirable	^Citation97
Datir et al	2012	MWCNT	Hyaluronic acid	Doxorubicin	A549	The hopeful result was observed	^Citation99
Arya et al	2013	SWCNT	Graphene oxide	paclitaxel	NCI-H460, and A549	Treatment was effective	^Citation88
Lodhi et al	2013	MWCNT	Just carboxylate	Dexamethasone	A549	Approach was more toxic for A549	^Citation100
Das et al	2013	MWCNT	Fluorochrome	Methotrexate	A549	The hopeful result was observed	^Citation101
Li et al	2014	MWCNT	….	Platinum	Mice lungs in vivo	Results confirmed that MWCNT are efficient nan-carrier	^Citation103
Tan et al	2014	MWCNT	Just carboxylate	Betulinic acid	A549	The drug was used in low concentrations and the results were positive	^Citation104
Zakaria et al	2015	SWCNT	pyrene butyric acid N-hydroxysuccinimide ester, and Polyethylene glycol	TRAIL or Apo2L	H1703	Treatment was effective	^Citation90
Guo et al	2015	MWCNT	Cation	siRNA	Calu 6	Anti-tumor effects were seen	^Citation98
Yu et al	2016	SWCNT	Chitosan	paclitaxel	A549	Cell proliferation was inhibited	^Citation89
Al Faraj et al	2016	SWCNT	Polyvinylpyrrolidone	Doxorubicin	Mice lungs in vivo	Treatment was more effective	^Citation91
Razzazan et al	2016	SWCNT	Polyethylene glycol	Gemcitabine	A549 in vivo	Anti-tumor efficacy was seen	^Citation94
Pratap Singh et al	2016	MWCNT	Alpha-tocopheryl polyethylene glycol 1000 succinate	Docetaxel/coumarin-6	A549	Results confirmed that MWCNT are efficient nan-carrier	^Citation105
Pratap Singh et al	2016	MWCNT	Alpha-tocopheryl polyethylene glycol 1000 succinate	Docetaxel/coumarin-6	A549	Efficacy with safety was seen	^Citation106
Kim et al	2017	MWCNT	Polyethylene glycol	….	Mitochondria in lung cancer cells (A549, and NHFB)	Anti-lung cancer efficacy was seen	^Citation86
Attri et al	2017	MWCNT	Graphene oxide	….	A549, and H460	The hopeful result was observed	^Citation95
Pratap Singh et al	2017	MWCNT	Chitosan	Docetaxel/coumarin-6	A549	Results were desirable	^Citation107
Heger et al	2017	MWCNT	Polyethylene glycol	VP-16 and Bcl-2-targeted antisense	DMS53, and NCIH2135	Hypersensitivity to this drug was observed	^Citation108
Su et al	2017	MWCNT	Polyethyleneimine	iRGD	A549	Treatment was effective	^Citation109
Neha et al	2018	SWCNT	Chitosan	Curcumin	A549	Cell proliferation was inhibited and apoptosis was induced	^Citation92
Suo et al	2018	MWCNT	Polyethylene glycol	….	Multi-drug resistance cells	The hopeful result was observed	^Citation96
Cao et al	2019	SWCNT	Polyethylenimine with betaine	Survivin siRNA, and Doxorubicin	A549 (in vitro/in vivo)	Anti-tumor effects were seen	^Citation93
Giuseppe Cirillo et al	2019	MWCNT	Chitosan	Methotrexate	MRC-5, and H1299	Less toxicity for healthy cells and more anti-tumor effect were confirmed	^Citation102

Notes: A brief description of the cells mentioned: (A549, NCI-H460, H1703, Calu 6, NHFB, H460, NCIH2135, and H1299 are non-small cell lung cancer cell lines), (DMS53 is small cell lung cancer cell line), (MRC-5 is fibroblast cell line).

Figure 4 Targeted and non-targeted treatment differences. Indeed, the figure refers to the accumulation of drug to the target cell. The drug is not distributed freely in nano-drug delivery.

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