Theranostic applications of multifunctional carbon nanomaterials

Abstract

Nanobiotechnology is one of the leading research areas in biomedical science, developing rapidly worldwide. Among various types of nanoparticles, carbon nanomaterials (CNMs) have attracted a great deal of attention from the scientific community, especially with respect to their prospective application in the field of disease diagnosis and therapy. The unique features of these nanomaterials, including favorable size, high surface area, and electrical, structural, optical, and chemical properties, have provided an excellent opportunity for their utilization in theranostic systems. Carbon nanotubes, carbon quantum dots, graphene, and fullerene are the most employed CNMs in biomedical fields. They have been considered safe and efficient for non-invasive diagnostic techniques such as fluorescence imaging, magnetic resonance imaging, and biosensors. Various functionalized CNMs exhibit a great capacity to improve cell targeting of anti-cancer drugs. Due to their thermal properties, they have been extensively used in cancer photothermal and photodynamic therapy assisted by laser irradiation and CNMs. CNMs also can cross the blood-brain barrier and have the potential to treat various brain disorders, for instance, neurodegenerative diseases, by removing amyloid fibrils. This review has summarized and emphasized on biomedical application of CNMs and their recent advances in diagnosis and therapy.

Keywords: carbon nanotube; carbon quantum dots; diagnosis; fullerene; graphene; therapy.

FIGURE 1

Carbon-based nanomaterials: (A) carbon nanotubes, (B) Carbon quantum dots, (C) graphene, and (D) fullerene.

FIGURE 2

In vivo magnetic resonance imaging (MRI) artifact assessment using carbon nanotubes (CNTs). (A) Schematic diagram of a rat implanted contralaterally with a CNT fiber and PtIr microwire used for MRI studies. (B–D) Horizontal (B), sagittal (C), and coronal (D) sections of the T2-weighted images of a rat implanted contralaterally with a Parylene-C-insulated CNT fiber and PtIr microwire. The insets are zoomed-in photographs of the red or blue boxes. Scale bar, 1.5 mm. The CNT fiber and PtIr microwire are in different planes in the sagittal and coronal images. (E) Coronal section of the T1-weighted image of the rat implanted contralaterally with a Parylene-C-insulated CNT fiber and PtIr microwire. The red and blue dashed boxes/arrows mark the CNT fiber and PtIr microwire, respectively. (F) MRI artifact size of the Parylene-C-insulated CNT fibers and PtIr microwires. The black dashed line denotes their actual size. CNT fibers are invisible in T1-weighted images. Error bars denote SEM, n = 5. ***p < 0.001; one-way analysis of variance (ANOVA). All CNT fibers and PtIr microwires used here are insulated with ~2.5 μm Parylene-C. Reproduced with permissions. Copyright ^© 2019, American Chemical Society.

FIGURE 3

A novel multifunctional hybrid nanoparticle platform fabricated from magnetic mesoporous silica gated with doped carbon dot for site-specific drug delivery, fluorescence, and magnetic resonance (MR) imaging. Reproduced with permissions. Copyright^© 2018, American Chemical Society.

FIGURE 4

Fluorescence bioimaging of carbon quantum dots (CQDs). (A) Toxicity assay of C. elegans incubation with nitrogen-doped CQDs (N-CQDs) at different concentrations prepared from P. acidus fruit. Multicolor in vivo model C. elegans incubation with N-CQDs prepared from P. acidus fruit imaging under the excitation of (B) 400 nm, (C) 470 nm, (D) 550 nm, (E) bright field (BF), and (F) merge (overlap). Live C. elegans were immobilized using 0.05% sodium azide (NaN3) for imaging under fluorescence filters (G) In vivo fluorescence imaging of graphene oxide-polyethyleneglycol (GO-PEG)-folate. Near-infrared (NIR) fluorescence images from phosphate-buffered saline (PBS) (left) and GO-PEG-folate (right) mice at 24 h after intravenous injection. (H) Tumor-to-background ratio (TBR) integrated from the NIR fluorescence images for both PBS and GO-PEG-folate, respectively. Reproduced with permissions.^, Copyright^© 2019 Elsevier B.V., and ^©2016 Elsevier Ltd.

FIGURE 5

Schematic view of the stepwise fabrication of immunosensor and the mechanism of detection. Reproduced with permission. Copyright^© 2018 Elsevier B.V.

FIGURE 6

Carbon nanotube (CNT)-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biosensor. Steps of fabrication of SARS-CoV-2 variable importance of projection (VIP) biosensor using CNTs combined with tungsten oxide (CNTs/WO3)-screen printed electrodes for imprinting the complete virus particles and testing the designed sensor for clinical sample analysis. Reproduced with permission. Copyright^© 2021 American Chemical Society.

FIGURE 7

Stepwise process of fabricating the nanohybrid electrochemical DNA biosensor to detect Mycobacterium tuberculosis (MTB). Reproduced with permission. Copyright^© 2019 Elsevier B.V.

FIGURE 8

Biodistribution of dye-conjugated single-walled carbon nanotubes (SWCNTs) for photothermal therapy (PTT) of cancer. (A) In vivo continuous observations (48 h) of mice administered SWNT-CY7-IGF-1Ra via the tail vein. The black dotted circle represents the location of the pancreatic carcinoma in situ. (B) Ex vivo imaging of tumor and major organs. H: heart. Li: liver. P: pancreas. T: tumor. S: spleen. Lu: lung. K: kidney. In: intestine. (C) Comparison of tumor-to-background ratio (TBR) profiles of the nanoprobes. The peak was 18 h post-injection, implying an optimal experimental window. (D) Fluorescence intensity of different tissues. Data represent the mean ± SD of triplicate experiments. (E) The accumulation of as-prepared nanotubes along the tumor blood vessels and at the normal-tumor tissue junction at 18 h post-injection. The as-prepared nanotubes appear as green fluorescent dots at 488 nm, and the blood vessels are shown as red fluorescent regions at 660 nm. The scale bar is 20 μm *p < 0.05, **p < 0.01, ***p < 0.001. Reproduced with permissions. Copyright^© 2019 Elsevier Ltd.

FIGURE 9

Proposed schematic diagram of carbon nanomaterial-based drug delivery to the brain.

FIGURE 10

A carbon nanotube (CNT)-based theranostic nanoplatform for Alzheimer’s disease (AD) treatment (A) Upconversion nanoparticle (UCNP@C60-pep) inhibited Aβ aggregation in vivo and attenuated the oxidative stress to prolong the lifespan of Caenorhabditis elegans (CL2006) strain. UCNP@C60-pep produced reactive oxygen species (ROS) under near-infrared (NIR) to disturb Aβ aggregation and scavenged the overproduced ROS in the dark. As a result, UCNP@C60-pep could ameliorate Aβ-triggered paralysis in CL2006 worms. (B) Representative ThS-staining images of N2 and UCNPs-treated CL2006 strains on the sixth day after the addition of the UCNPs. The wild-type N2 strain was used as the control. Scale bars are 40 μm. (C) The ROS level of worms was detected by DCF fluorescence on the sixth day. (D) Survival curves of UCNPs-treated CL2006 strain. Strains were classified as paralyzed if they failed to respond to a touch-provoked movement. Reproduced with permission. Copyright^© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FIGURE 11

Schemes of the caterpillar-like soft robot. (A) The crawling mechanism of a caterpillar in nature. (B) Schematic diagram of the caterpillar-like soft robot composed of three layers. (C) The crawling process of the soft robot is driven by cardiomyocytes. Reproduced with permission. Copyright^© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FIGURE 12

Composite scaffolds in cardiac tissue engineering. (A–C) Images of rat cardiac tissue (A) Brightfield images of polymers seeded with rat CMs (Scale bars: 100 μm). (B) Tissues viability images using live/dead staining assay (Live cells: green, dead cells: red) (Scale bars: 100 μm). (C) High magnification of wrapping of viable cells around scaffold struts (Scale bars: 50 μm). (D) Cell viability quantification of live-dead images. (E) Comparison of excitation threshold (F) and maximum capture rate (*p < 0.05). (G) Adsorption configuration, Frontier molecular orbital (FMO), electron localization function (ELF), and DOS plots of NPX/Ca(C20) adsorption complex. (H,K) Assessment of in vivo cardiac functions of infarcted hearts after treatment with hydrogel combined with BADSCs. Representative echocardiography images of MI model rat in (H) blank group, (I) phosphate-buffered saline (PBS)+BADSCs group, (J) Alg+BADSCs group, and (K) fullerenol/Alg+BADSCs group. Reproduced with permissions from references.^,– Copyright^© 2016 Acta Materialia Inc. Published by Elsevier Ltd., ^© 2022 Elsevier B.V., and ^© 2017, American Chemical Society.