Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction

Abstract

Within phototherapy, a grand challenge in clinical cancer treatments is to develop a simple, cost-effective, and biocompatible approach to treat this disease using ultra-low doses of light. Carbon-based materials (CBM), such as graphene oxide (GO), reduced GO (r-GO), graphene quantum dots (GQDs), and carbon dots (C-DOTs), are rapidly emerging as a new class of therapeutic materials against cancer. This review summarizes the progress made in recent years regarding the applications of CBM in photodynamic (PDT) and photothermal (PTT) therapies for tumor destruction. The current understanding of the performance of modified CBM, hybrids and composites, is also addressed. This approach seeks to achieve an enhanced antitumor action by improving and modulating the properties of CBM to treat various types of cancer. Metal oxides, organic molecules, biopolymers, therapeutic drugs, among others, have been combined with CBM to treat cancer by PDT, PTT, or synergistic therapies.

Keywords: cancer; carbon dots; graphene oxide; graphene quantum dots; phototherapy; reduced graphene oxide.

Figure 2

Materials used for the surface modification of GO. Reproduced from Ref. [59]. Copyright 2021 Springer Nature.

Figure 1

CBM: (a) Graphene with sp²-hybridized carbon atoms; (b) GO; (c) r-GO and (d) GQD. Reproduced from Ref. [50]. Copyright 2017 MDPI.

Figure 3

PS molecules of Chlorin e6 (Ce6) loaded by folic acid-conjugated GO for PDT applications in cells. Reproduced from Ref. [63]. Copyright 2012 PubMed Central.

Figure 4

(A) TEM image of the composite; (B) Composite particle size distribution (DLS); (C) Photothermal effect curves of the composite, IR820-LA, GO, and water under a 660 nm laser (n = 3); and (D) In vitro DOX drug release of the composite. Complex* correspond to GO/DOX/IR820-LA composite. Reproduced from Ref. [67]. Copyright 2019 ELSEVIER.

Figure 5

Procedure to apply GO-based hybrids/composites in PDT, PTT, and targeted drug delivery. EPR: enhanced permeability and retention. Reproduced from Ref. [58]. Copyright 2020 MDPI.

Figure 6

TEM images of (a) GO; and its reduction to r-GO at different temperatures: (b) 250 °C, (c) 300 °C, (d) 400 °C, and (e) 500 °C. Reproduced from Ref. [73]. Copyright 2020 ELSEVIER.

Figure 7

Applications of r-GO in PDT and PTT, chemotherapy/phototherapy, photothermal/immune therapy, gene therapy, and chemotherapy. Reproduced from Ref. [76]. Copyright 2021 MDPI.

Figure 8

SEM images of: (a) CMC/r-GO powder; (b) CMC/CHO/PEG hydrogel; (c) CMC/r-GO/CHO/PEG hydrogel; and (d) illustration of CMC/r-GO/CHO/PEG hydrogel. The insets show photographs of the corresponding samples. Reproduced from Ref. [82]. Copyright 2019 ELSEVIER.

Figure 9

(A) IR thermal images of A549 tumor-bearing mice exposed to 808 nm laser for 5 min. (B) Tumor growth curves of different groups of A549 tumor-bearing mice (n = 5). (C) Photos of mice after various treatments taken on day 15. Reproduced from Ref. [86]. Copyright 2017 ACS.

Figure 10

GQDs related inherent effects, preparation methods, properties, and applications. Reproduced from Ref. [53]. Copyright 2018 ELSEVIER.

Figure 11

(a) Tumor thermal images of temperature variations after intravenous injection of saline and IR780/GQDs-FA with laser irradiation; (b) Photos of the tumor-bearing mice after treatments. Tumor volume (c) and body weight (d) curves of the tumor-bearing mice. (e) Histological evaluation of tissues from the mice treated with saline and IR780/GQDs-FA. Each organ was sliced for hematoxylin and eosin (H&E) staining. Reproduced from Ref. [102]. Copyright 2017 ACS.

Figure 12

Morphological analysis of GQDs from withered leaves. TEM image of (A) ultra-small GQDs and (B) existence of GQDs in cluster form with inset showing size distribution. (C) HRTEM of a single crystalline GQD (marked in (B)) with a honey-comb-like structure of graphene with few basal/edge state-defects shown with an arrow. Inset here shows lattice spacing distance. (D) Ball and stick model indicating the defect in a typical structure of GQD with self-passivated functional groups. Reproduced from Ref. [105]. Copyright 2017 Royal Society of Chemistry.

Figure 13

Schematic diagram of PDT. C-DOTs (CDs) penetrate the cell membrane and accumulate in the cytosol. Light irradiation actives and induces the production of ROS. Reproduced from Ref. [116]. Copyright 2021 MDPI.

Figure 14

(a) Temperature curves of C-DOTs solution (20 mg/mL); (b) Temperature curves of different concentrations of C-DOTs solutions; (c) Photothermal profiles of C-DOTs solution with 3 irradiation cycles; (d) Thermal infrared images of C-DOTs solutions recorded after 7 min of irradiation; (e) Heating and cooling curves of C-DOTs solution; (f) Linear time data and −ln θ acquired from a cooling period of (e). 1.4 W cm⁻²; 15 mg/mL. Reproduced from Ref. [121]. Copyright 2019 ACS.

Figure 15

Lysosome targetable C-DOTS which can simultaneously generate ¹O₂, OH^●, and heat under 635 nm laser irradiation. Reproduced from Ref. [123]. Copyright 2020 ELSEVIER.

Figure 16

Representative mice images showing the sizes of tumors at pre-treatment day, 5th day, and euthanasia day under 808 nm, 1.8 W/cm² for light, ICG, GO+PEGFA+RhodB, and GO+PEGFA+ICG mice groups. Reproduced from Ref. [72]. Copyright 2021 PMC.

Figure 17

(a) CBM can be described by the dimensions and surface functionalization of the material (percentage of the carbon atoms in sp³ hybridization). Green squares represent epitaxially grown graphene; yellow, mechanically exfoliated graphene; red, chemically exfoliated graphene; blue, GO. (b) Possible interactions between CBM with cells (a) Adhesion onto the outer surface of the cell membrane. (b) Incorporation in between the monolayers of the plasma membrane lipid bilayer. (c) Translocation of the membrane. (d) Cytoplasmic internalization. (e) Clathrin-mediated endocytosis. (f) Endosomal or phagosomal internalization. (g) Lysosomal or other perinuclear compartment localization. (h) Exosomal localization. The biological outcomes from such interactions can be considered to be either adverse or beneficial, depending on the context of the particular biomedical application. Different CBM will have different preferential mechanisms of interaction with cells and tissues that largely await discovery. Reproduced from Ref. [135]. Copyright 2014 the American Association for the Advancement of Science.

Figure 18

Schematic diagram showing the possible mechanisms of CBM cytotoxicity. CBM get into cells, which induces ROS generation, lactate dehydrogenase and malondialdehyde increase, and Ca²⁺ release. Subsequently, CBM cause kinds of cell injury, for instance, cell membrane damage, inflammation, DNA damage, mitochondrial disorders, apoptosis, or necrosis. Reproduced from Ref. [141]. Copyright 2016 Springer Nature.