Applications of Pristine and Functionalized Carbon Nanotubes, Graphene, and Graphene Nanoribbons in Biomedicine

Abstract

This review is dedicated to a comprehensive description of the latest achievements in the chemical functionalization routes and applications of carbon nanomaterials (CNMs), such as carbon nanotubes, graphene, and graphene nanoribbons. The review starts from the description of noncovalent and covalent exohedral modification approaches, as well as an endohedral functionalization method. After that, the methods to improve the functionalities of CNMs are highlighted. These methods include the functionalization for improving the hydrophilicity, biocompatibility, blood circulation time and tumor accumulation, and the cellular uptake and selectivity. The main part of this review includes the description of the applications of functionalized CNMs in bioimaging, drug delivery, and biosensors. Then, the toxicity studies of CNMs are highlighted. Finally, the further directions of the development of the field are presented.

Keywords: bioimaging; biological applications; biosensing; carbon nanotubes; drug delivery; functionalization; graphene; graphene nanoribbons; nanomaterial toxicity.

Figure 1

A schematic representation of different types of chemical functionalization of CNMs.

Figure 2

Main directions to improve the functionality of CNMs in biomedicine. Reprinted from [65]. Copyright 2018, with permission from Elsevier.

Figure 3

The primary application of graphene-based nanomaterials in biomedicine: bioimaging, drug delivery, biosensing. Some of the included images were adapted with permission from [104,105]. Copyright 2013, American Chemical Society. Copyright 2016, with permission from Elsevier.

Figure 4

Whole-body SPECT/CT imaging and quantitative $$\gamma$$-counting that were used to study the pharmacokinetics and biodistribution of $${}^{153}$$Sm@SWCNTs and $${}^{153}$$Sm@MWCNTs up to 24 h. (a) SPECT/CT imaging, (b) blood circulation, (c) excretion profiles, and (d) tissue biodistribution profiles. Reprinted with permission from [111]. Copyright 2020, American Chemical Society.

Figure 5

Fluorescent images of human breast cancer cells T47D after incubation with green GQDs for 4 h. (a) Phase contrast picture of T47D cells. (b) Individual nucleus stained blue with DAPI. (c) Agglomerated green GQDs surrounding each nucleus. (d) The overlay high-contrast image of the nucleolus stained with blue DAPI and GQD (green) staining. Reprinted with permission from [156]. Copyright 2012, American Chemical Society.

Figure 6

(a) In vivo behaviors of $${}^{131}$$I–rGO–PEG. Gamma imaging of mice bearing 4T1 tumors after i.v. injection of $${}^{131}$$I–rGO–PEG and free $${}^{131}$$I at the same radioactivity dose. $${}^{131}$$I–rGO–PEG can passively accumulate in the tumor via the enhanced permeability and retention (EPR) effect, while $${}^{131}$$I can only be rapidly excreted from the body. Tumors are highlighted by circles in X-ray imaging and arrows in gamma imaging [164]. Copyright 2015, with permission from Elsevier. (b) Photoacoustic images of NGO–PEG, rNGO–PEG, NGO–PEG/ICG, and rNGO–PEG/ICG with the same GO concentration and whole blood. (c) Photoacoustic and FL images of rNGO–PEG/ICG covered with 5 mm-thick agarose gel containing 0.5% intralipid. (d) White light (WL), FL, and PA MAP images of a PE tube filled with rNGO–PEG/ICG. (e) White light, FL, and PA MAP images of a mouse with the rNGO–PEG/ICG-filled PE tube implanted subcutaneously at the dorsal aspect of the leg. The white dashed box indicates the location of the tube [169].

Figure 7

SARS-CoV-2 detection scheme using GFETError. Reprinted with permission from [224]. Copyright 2020, American Chemical Society.

Figure 8

(a) The uptake of GONR–PEG–DSPE into U251 cells in large vesicular structures (black arrow); (b) the uptake of small aggregates of GONR–PEG–DSPE into U251 cells (black arrow); (c) no or minimal uptake of GONR–PEG–DSPE into MCF-7 cells (black arrow); (d) large aggregates outside of the MCF-7 cells (black arrow) [231]. Copyright 2015, with permission from Elsevier.

Figure 9

(a) NIR thermal images of water, PL–PEG–GONR, and DOX-loaded PL–PEG–GONR; (b) graph showing 120 s NIR irradiation with increasing temperature; (c) bright field (left), fluorescence (middle) and merged micrographs (right) of U87 cells after treatment with PL–PEG–GONRs/DOX for 6 h observed by confocal laser scanning microscopy [232]. Copyright 2014, with permission from Elsevier.