Cancer Targeting and Diagnosis: Recent Trends with Carbon Nanotubes

Abstract

Cancer belongs to a category of disorders characterized by uncontrolled cell development with the potential to invade other bodily organs, resulting in an estimated 10 million deaths globally in 2020. With advancements in nanotechnology-based systems, biomedical applications of nanomaterials are attracting increasing interest as prospective vehicles for targeted cancer therapy and enhancing treatment results. In this context, carbon nanotubes (CNTs) have recently garnered a great deal of interest in the field of cancer diagnosis and treatment due to various factors such as biocompatibility, thermodynamic properties, and varied functionalization. In the present review, we will discuss recent advancements regarding CNT contributions to cancer diagnosis and therapy. Various sensing strategies like electrochemical, colorimetric, plasmonic, and immunosensing are discussed in detail. In the next section, therapy techniques like photothermal therapy, photodynamic therapy, drug targeting, gene therapy, and immunotherapy are also explained in-depth. The toxicological aspect of CNTs for biomedical application will also be discussed in order to ensure the safe real-life and clinical use of CNTs.

Keywords: carbon nanotubes; electrochemical sensing; gene therapy; immunotherapy; photoacoustic imaging; photodymanic therapy; photothermal therapy.

Figure 1

Schematic showing the advantages and disadvantages of carbon nanotubes.

Figure 2

Schematic of the functionalization of SWCNTs and MWCNTs through covalent or noncovalent binding. Reprinted with permission from Life Sciences, Copyright 2020, Elsevier [1].

Figure 3

A roadmap for the evolution in the use of carbon nanotubes in cancer targeting and diagnosis.

Figure 4

The schematic diagram of the smartphone-based differential pulse amperometry system. Reprinted with permission from Biosensors and Bioelectronics, Copyright 2019, Elsevier [27].

Figure 5

(a) Oxidation of levodopa on the surface of the modified working electrode. (b) The scanning electron microscope image of the bare screen-printed electrode. (c) The scanning electron microscope image of the gold nanoparticle/single-wall carbon nanotube/chitosan-film on the screen-printed electrode. (d) Cyclic voltammetry of the redox couple at different electrodes. Reprinted with permission from Biosensors and Bioelectronics, Copyright 2019, Elsevier [27].

Figure 6

Schematic of the multi-walled carbon nanotube-based electrochemical sensor. Reprinted with permission from Michrochemical Journal, Copyright 2022, Elsevier [28].

Figure 7

(A) Illustration of double CNT functionalization. (B) Optical spectra of plain SWNT. (C) Photoacoustic (PA) detection of SWNT-ICG in living mice at different concentrations. (D) Correlation between the functionalized CNT concentration and the corresponding PA signal. Reprinted with permission from Nano Letters, Copyright 2010, American Chemical Society [43].

Figure 8

Effect of CNTs during plasmonic biosensing. Reprinted with permission from Biosensors and Bioelectronics, Copyright 2017, Elsevier [52].

Figure 9

(A) Schematic representation of CNT-PEG-PEI nanocarriers and the drug-loading process. (B) (a) Fluorescence images of MCF-7 cells after treatment with free DOX (control) and different DOX-loaded nanocarrier formulations for 12 h. (b) Fluorescence intensity of free DOX and different DOX-loaded nanocarrier formulations (n = 3). Student t-test was used for statistical analysis. (C) (a) Confocal microscopy images of MCF-7 cells after treatment with free DOX (control) and different DOX-loaded nanocarrier formulations for 12 h. (b) Quantitative fluorescence intensity of free DOX and different DOX-loaded nanocarrier formulations (n = 3). Student t-test was used for statistical analysis [75].

Figure 10

(A) MTT viability assay of HeLa cells treated with free DOX and MWCNT/PEI–FI–HA/DOX complexes at the DOX concentrations of 0–4 μM for 24 h, and (B) DOX-free MWCNT/PEI–FI–HA at corresponding DOX concentrations of the complexes between 1.25 and 10 mg/L. (C) Confocal microscopic images of HeLa and L929 cells treated with MWCNT/PEI–FI–HA/DOX complexes ([DOX] = 2 μM) for 2 h. HeLa and L929 cells treated with PBS were used as controls. The scale bar in each panel represents 20 μm. Reprinted with permission from Carbohydrate Research, Copyright 2015, Elsevier [78]. *** represents the significant level p < 0.001.

Figure 11

(A) Schematic diagram of the temperature-sensitive CNT-PS/siRNA nanoparticle for the synergistic PTT and GT of cancer cells. (B) In vivo anti-tumor study. (a) Treatment procedure. (b) Growth curves of tumors over the course of 21 days after various treatments (n = 5 for each group). Each group was treated with the lipid-coated CNT–siRNA complexes ([CNT] = 3 mg/kg, [siRNA] = 1.5 mg/kg) by intravenous injection every 4 days. For groups with PTT treatment, tumor sites were irradiated with an 808 nm NIR laser at 1 W/cm² for 5 min at 4 h after injection. After irradiation, the tumor tissue was found to be 42–45 °C. Mice with PBS injection were used as the control group without any further treatment (mean ± SD, n = 5). ** p < 0.01; *** p < 0.001. (c) Representative images of harvested tumors after 21 days of treatment. (d) Representative images of mice after the different treatments. One mouse was randomly selected from each group. Scale bar: 1 cm. (e) In vivo apoptosis of tumor cells was evaluated by the TUNEL assay (nuclei are stained using DAPI, apoptotic cells are green). Scale bar: 100 μm. Reprinted with permission from ACS Nano, Copyright 2021, American Chemical Society [87].

Figure 12

(A) Schematic diagram of DOX–SPBB–siRNA nanocarriers in A549 lung cancer cells. (B) CLSM images of A549 cells treated with DOX–SPBB–siRNA for 2 and 4 h at given concentrations of DOX (2 μg/mL) and FAM–siRNA (80 nM). Each column from left to right: nuclei stained with Hoechst 33342 (blue); DOX fluorescence in cells (red); FAM signal in cells (green); DOX and FAM-siRNA merged with nucleus. (C) In vivo antitumor ability of SPBB loaded with DTX and/or siRNA in A549 tumor-bearing nude mice. (a) Appearance of tumor growth. (b) Changes in body weight. (c) Changes in relative tumor volumes. (d) Tumor tissues after being treated for 10 days (n = 6, mean ± SD). Reprinted with permission from Applied Materials, Copyright 2019, American Chemical Society [93]. ** p < 0.01; *** p < 0.001.

Figure 13

(A) Synthetic routes for (a) ZnMCPPc-spermine-SWCNT (2) and (b) ZnMCPPc-spermine-SWCNT (3). Reprinted with permission from Synthetic Metals, Copyright 2015, Elsevier [106]. (B) Microscopic images of untreated and treated cells. (a) Group 1 cells (untreated) at 0 h and 24 h, (b) Group 2 cells (5 J/cm²) at 0 h and 24 h (c) Group 3 (10 J/cm²) cells at 0 h and 24 h. Scale bar represents 100 μm. Black arrow indicates the cellular death. (C) The cytotoxicity effects of SWCNTs, Ce6, SWCNT-HA-Ce6 on Caco-2 cells determined by LDH assay. Significance is shown as * p < 0.05; ** p < 0.01; *** p 0.001 [108].