Table 1.
Various bioactives delivered through functionalized CNTs for pharmaceutical and biomedical applications
| Functionalized CNTs | Cell lines used | Bioactives agents used | Physicochemical/biological parameters | Outcomes of the study | References |
|---|---|---|---|---|---|
| FITC-MWCNTs & Oxidized MWCNTs | Human Jurkat T lymphoma cells | Amphotericin B (AmB) via covalent attachment | Electron microscopy Antifungal activity |
AmB covalently linked to CNTs is taken up by mammalian cells devoid any specific toxic effect. f-CNTs are able to enter the cell by a spontaneous mechanism. | [34] |
| PL-PEG-FA & PL-PEG-FITC-SWCNTs. | HeLa cells | Cy3-labeled DNA | Atomic force microscopy Confocal laser scanning microscopy |
SWCNTs internalized in living cells can act as tiny NIR ‘heaters’ or ‘antennas’. | [10] |
| PL-PEG-RGD-SWCNT & FITC annexin V-SWCNTs. | MCF-7 breast cancer and U87 MG cancer cell lines | Doxorubicin | Fluorescence Supramolecular loading efficiency |
Enhanced uptake of DOX in case of integrin-positive U87 MG using RGD-based targeting relative to integrin-negative MCF-7 Cells. | [40] |
| PL-PEG-SWCNTs | NTera-2 | Cisplatin prodrug conjugate | Fluorescence microscopy | Cytotoxicity of the free platinum(IV) complex increases by >100-fold when the complex is attached to the surface of the functionalized SWNTs. | [41] |
| Pluronic F 127 stabilized-MWCNTs | MCF-7 human breast cancer cells | Doxorubicin through π–π stacking | Electron microscopy Confocal laser microscopy |
Enhanced cytotoxicity of DOX-MWCNTs complex over free DOX. | [42] |
|
DSPE-PEG5000-PTX-SWCNTs PEG- SWCNTs. |
4T1 tumor-bearing mice (tumor size, ∼200 mm3). | Paclitaxel (PTX) | Pharmacokinetics and biodistribution study Antitumor efficacy Pilot toxicity study |
Water-soluble SWCNTs-PTX formulation is cremophor-free. SWCNTs have shown to be safe at least in mouse models. |
[43] |
| CNTs | Bladder cancer cells | Carboplatin | Electron energy loss spectroscopy X-ray-photoelectron spectroscopy Cell proliferation Cytotoxicity |
High efficacy of carboplatin filled CNTs with reduced growth of bladder cancer cells compared to free drug CNTs. | [44] |
| Folic acid (FA)-chitosan (CHI)/alginate (ALG)-SWCNTs. | HeLa cell line | Doxorubicin through π–π stacking. | Fluorescence Cell viability and cell uptake studies |
CNTs complex found to be more selective and effective than free DOX due to targeting based on FA and release of DOX at lysosomal pH. | [45] |
| mAB-BSA adsorbed-SWCNTs. | WPDr colon cancer cell line | Doxorubicin through π–π stacking. | Electron microscopy (SEM, HRTEM) Raman spectroscopy |
Uptake study revealed that delivery efficiency was 100%. All cells could take up the SWCNT complexes. |
[46] |
| Diaminotriethylene glycol-MWCNTs. | MKN-28 cells and H22 cell lines | 10-Hydroxycamptothecin (HCPT) through π–π stacking. |
In vitro single photon emission computed tomography (SPECT). ex vivo gamma scintillation counting analysis |
MWCNTs-HCPT conjugate enhanced superior antitumor activity both in vitro and in vivo to clinical HCPT formulation. They show relatively long blood circulation and high drug accumulation at the tumor site. | [47] |
| Dapsone-MWCNTs-FITC | Subvert normal macrophage (MØ) and PMØ | Dapsone (DDS) | Confocal laser microscopy Phagocytosis assay |
Dapsone-MWCNTs did not trigger oxidative stress but caused apoptosis of PMØ predominantly after prolonged cultivation (3 days). | [48] |
| Azomethine ylide (1.3-dipolar cycloaddition)-MWCNTs. | MCF-7 Cell line. | Methotrexate (MTX) through cleavable ester bond. | Electron microscopy Cytotoxicity study |
Cytotoxic activity of CNTs conjugate was strongly dependent on the presence and type of linker. | [49] |
| EGF-SWCNTs–cisplatin–EGF | Head and Neck Squamous Carcinoma Cells (HNSCC), HN12 cells |
Cisplatin | Histological analysis Raman analysis Annexin V assay |
PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors. | [50] |
| Sgc8c aptamer-SWCNTs | Molt-4 (Target) and U266 non-target (B lymphocyte human myeloma) cell line | Daunorubicin (anthracycline antibiotic) through π–π stacking | Cell viability Loading efficiency ∼157% Flow cytometry analysis |
Dau-aptamer-SWCNTs complex was able to selectively target Molt-4 cells compared to non target cells. | [51] |
| CNT-PEI and CNT-pyridinium-MWCNTs | Human lung cancer cells (H1299) | siRNA | Gene silencing and cytotoxicity agarose gel electrophoresis | CNT-PEI and CNT-pyridinium did not show any added value over PEI, pDMAEMA, and Lipofectamine used as reference transfection agents for siRNA silencing activity and cytotoxicity. | [52] |
| Hyaluronate tethered MWCNTs | A 549 cell line | Doxorubicin (DOX) | Pharmacodynamic and organ distribution studies Tumor growth inhibition studies Apoptosis study Cytotoxicity study |
The 99mTc-MWCNT-HA-DOX is significantly higher than both free drug and non-targeted MWCNTs in organ distribution studies on Ehlrich ascites tumor (EAT) bearing mice. The tumor-growth inhibitory effect of HA-MWCNTs-DOX was found to be 5 times higher than free DOX in chemically breast-cancer-induced model in pharmacodynamic studies devoid of any detectable cardiotoxity, hepatotoxicity, or nephrotoxicity. |
[53] |
| DOX-FA-MN-MWCNT | U87 cell lines | Doxorubicin | Electron microscopy CLSM. |
Dual targeted DOX-FA-MN-MWCNTs showed the high drug loading, pH-dependent controlled release, magnetic targeting, and ligand–receptor interactions. | [37] |
| AmB/Mannose-MWCNTs | J774 cells | Amphotericin B (AmB) | CLSM In vitro & in vivo studies macrophage uptake study |
AmBitubes showed better targeting efficiency to macrophages i.e. J 774 cell lines with reduced toxic effects associated with AmB. | [36] |
| DOX/DEX-MWCNTs | A-549 cells | Doxorubicin (DOX) | In vitro & ex vivo studies | DOX/DEX-MWCNTs found less hemolytic and more cytotoxic as compared to free DOX on A-549 lung epithelial cancer cell line. | [38] |
| Functionalized MWCNTs | Raw 264.7 and A-549 cell lines | – | Immunofluorescence microscopy | The chemical functionalization tailors the fate of CNTs by tilting the balance toward specific mechanisms of internalization, cellular processing and elimination/degradation. | [13] |
| Angiopeptide conjugated PEGylated oxidized MWCNTs | Brain capillary endothelial cells (BCEC) and C6 glioma cells | Doxorubicin (DOX) | Anti-glioma efficacy Intracellular fluorescence distribution. Fluorescence imaging |
The results showed that DOX-O-MWCNTs-PEG-ANG is a promising dual-targeting carrier to deliver DOX for the treatment of brain tumor | [22] |
| f-SWCNTs-COS-GTX-p53 | HeLa and MCF-7 cells | Gliotoxin | Cytotoxicity study Fluorescent activated cell sorter analysis |
The f-SWCNTs-COS-GTX-p53 was found to be most effective delivery vehicle with a controlled release and enhanced cytotoxicity rendered through apoptosis in HeLa cells. | [54] |
| GL-MWCNTs-DOX | HepG2 cell | Doxorubicin | Electron microscopy Flow cytometry and phase contrast microscopy Anticancer activity |
GL-MWCNTs-DOX formulation approach was found to be promising toward development of an affluent liver targeting. | [55] |
MWCNTs: Multi walled carbon nanotubes; SWCNTs: Single walled carbon nanotubes; FITC: Fluorescence isothiocynate; PEI: Polyethyleneimine; PL-PEG: Phoshpholipid-Polyethlene glycol; RGD: Arginine-glycine-aspartic acid; NGR: Asn-Gly-Arg; HCPT: Hydroxycamptothecin; NIR: Near infrared; EGF: Epidermal growth factor; PL-PEG-FA: Phospholipid polyethylene glycol-folic acid; PEI: Polyethleneimine; siRNA: small interfering ribonucleic acid; Amphotericin B: AmB; GTX: Gliotoxin; GL: Glycyrrhizinic acid; DOX: Doxorubicin.