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Recently, photothermal therapy (PTT) has emerged as one of the most promising biomedical strategies for different areas in the biomedical field owing to its superior advantages, such as being noninvasive, target-specific and having fewer side effects. Graphene-based hydrogels (GGels), which have excellent mechanical and optical properties, high light-to-heat conversion efficiency, and good biocompatibility, have been intensively exploited as potential photothermal conversion materials.
- graphene integrated hydrogel
- photothermal biomedicine
- photothermal therapy
1. Introduction
Photothermal therapy (PTT) has emerged in the last few decades as a potential medical tool in the area of various diseases and medical therapy, such as cancer therapy [1][2][1,2], bacterial infection [3], bone regeneration and tissue engineering [4] and drug delivery [5]. PTT is one of the main types of phototherapeutic methods for disease treatment because of its localized ablation of the tissue of interest and minimal heating damage to normal tissues near the targeted tissues. The core principle of PTT is the application of external near-infrared (NIR) light, which is absorbed by highly efficient photothermal agents (PTAs) accumulated noninvasively within the targeted tissues to convert absorbed light into thermal energy, thereby increasing the kinetic energy to provide local overheating. Because the hypothermia effect occurs only in the presence of PTAs in the targeted tissues, PTT offers highly efficient and unique methods for disease treatment owing to its precise spatial-temporal effect, high sensitivity, high pharmacokinetics, few side effects, ease of manipulation, low invasive burden, speed and efficacy of treatment and low cost [6][7][6,7]. The primary prerequisite for an effective PTT is the efficient delivery of PTAs to the tissue of interest and to precisely direct the external light into the tissues where PTAs are located. To meet this requirement, the dominant strategy has been to create highly efficient and multifunctional nanomaterials as PTAs with sufficient photothermal conversion efficacy and high biocompatibility [8][9][10][8,9,10]. PTAs with high light absorption capacity, high photostability, minimal cytotoxicity and good biocompatibility are more favorable. It is also important to note that the PTA components, structures and size remarkably affect the pharmacokinetics of PTT, including drug absorption, distribution, metabolism and release [11][12][11,12]. Hence, highly integrated nanomaterials are crucial for enhancing the optical properties, particle stability and biocompatibility, while reducing undesirable effects or toxicity, especially for drug delivery and tumor therapy.
To date, a variety of NIR-responsive nanomaterials, including both organic [13][14][13,14] and inorganic agents [15][16][15,16] have been explored for PTA preparation. Among them, biomaterials with adequate biocompatibility are highly preferred. Hydrogels that possess the obligatory characteristics for biomedical applications, such as good biocompatibility and low toxicity, have been envisioned as a new promising class of PTAs [17][18][17,18]. A hydrogel is a group of polymeric materials that can form a three-dimensional (3D) network of hydrophilic soft polymers with several unique features, including hydrophilicity, viscosity, elasticity, high water content and tunable stiffness, making them able to be fashioned into specific level through manipulation with different crosslinker types [19][20][19,20]. Other excellent characteristics of hydrogels include their biodegradability [21] and ability to mimic the compositions and physicochemical properties of the natural extracellular matrix [22], making hydrogels a highly biocompatible material with negligible cytotoxicity [23]. Owing to these unique properties, significant research attention has been given to hydrogels in recent years for many applications in the field of biomedicine, such as tissue engineering [24], drug carriers [25], anticancer [26] and antibacterial therapies [27] and biosensors [28][29][28,29]. Notably, hydrogel-based systems have shown distinct advantages in PTT and intensive studies have been conducted to fabricate hydrogel-modified composites to enhance the efficacy of photothermal therapeutics [30][31][30,31]. Nevertheless, a major limitation of hydrogels is the lack of mechanical strength, making it a great challenge for therapeutic applications. One innovative strategy to overcome this issue is to incorporate other materials into hydrogels to precisely mimic the extracellular matrix and improve the composite stiffness [32]. Among the different nanomaterials, graphene and graphene-based nanocomposites have been proposed as a new promising class of photothermal materials and the incorporation of graphene into hydrogel networks has significantly improved the capacity of hydrogels owing to their superior mechanical, electrical and optical properties [33].
Graphene and its chemical derivatives graphene oxide (GO) and reduced GO (rGO) are two-dimensional carbon single layers that possess abundant functional groups on their surface (carboxyl and hydroxyl groups), novel physical properties (photothermal properties, photoluminescent properties and large specific surface area) and good biocompatibility [34]. Owing to these superior properties, graphene and graphene derivatives have sparked great attention for different applications in the field of biosensors, drug delivery and bioimaging [35][36][35,36]. Among different types of graphene, GO is a useful material for photothermal application and is commonly used as a basic building material for the fabrication of other graphene-based nanomaterials. GO nanosheets have been used as effective building blocks for improving the chemical and physical properties of new integrated nanocomposites, such as light absorption, thermal and electrical conductivity and flexibility [37]. Furthermore, graphene possesses strong optical absorption in the NIR regions [38], making it a promising candidate for photothermal applications compared to existing conventional photothermal materials. Owing to the aforementioned features of graphene and hydrogel, there have been increasing studies to explore graphene-based hydrogel (GGel) nanocomposites for NIR-mediated PTT. The existing GGels have exhibited improved physical, chemical and biological properties, making them great candidates as potential PTAs [39][40][39,40].
2. Thermal Property of Graphene-Integrated Hydrogels
Based on an inherently extraordinary structure, graphene can strongly interact with low-frequency photons and generate heat under specific wavelengths such as NIR light through plasmonic photothermal conversion [41]. Upon NIR irradiation, graphene surface plasmons are stimulated and induce random resonance and dipole transmission, which is required for the conversion of thermal photon energy output. The absorption spectra of graphene and GO show that absorbance of GO falls from UV to NIR region while graphene keeps constant absorbance (Figure 3a). To validate the higher thermal conductivity of graphene-based materials for photothermal application, photothermal conversion efficiencies of graphene, GO and Au nanorods were measured under illumination at different NIR wavelength (980, 808, 650 nm) using time constant and integrating sphere methods, respectively, exhibiting the higher photothermal efficiency of graphene and GO about 58–67% under 808 nm NIR irradiation compared to 52% of Au nanorods (Figure 3b) [42]. Hence, GGels also exhibit noticeable photon absorption under NIR irradiation, facilitating local temperature enhancement surrounding injected materials and killing cancerous cells.
Based on an inherently extraordinary structure, graphene can strongly interact with low-frequency photons and generate heat under specific wavelengths such as NIR light through plasmonic photothermal conversion [79]. Upon NIR irradiation, graphene surface plasmons are stimulated and induce random resonance and dipole transmission, which is required for the conversion of thermal photon energy output. The absorption spectra of graphene and GO show that absorbance of GO falls from UV to NIR region while graphene keeps constant absorbance (Figure 3a). To validate the higher thermal conductivity of graphene-based materials for photothermal application, photothermal conversion efficiencies of graphene, GO and Au nanorods were measured under illumination at different NIR wavelength (980, 808, 650 nm) using time constant and integrating sphere methods, respectively, exhibiting the higher photothermal efficiency of graphene and GO about 58–67% under 808 nm NIR irradiation compared to 52% of Au nanorods (Figure 3b) [80]. Hence, GGels also exhibit noticeable photon absorption under NIR irradiation, facilitating local temperature enhancement surrounding injected materials and killing cancerous cells.
Figure 3.
(
a
) Absorption spectra of graphene in dimethylformamide and GO in water in both visible and NIR range, inset is magnification of spectra from 650–1000 nm. (
b) Photothermal conversion efficiencies of graphene, GO and Au nanorods determined by time constant and integrating sphere methods. Adapted with permission from [42].
) Photothermal conversion efficiencies of graphene, GO and Au nanorods determined by time constant and integrating sphere methods. Adapted with permission from [80].
Currently, heating is widely used as an effective and useful method for cancer therapy due to the burning of cancerous cells and tumors upon the enhancement of biological molecular temperature. Additionally, for non-superficial treatments, irradiation by laser at NIR was extensively investigated to minimize damage to non-specific surrounding tissues [42]. Among the promising photothermal materials, graphene-incorporated materials have attracted much attention because of their outstanding properties, especially the high absorption of NIR. Therefore, graphene/derivative graphene-based materials have been employed in diverse applications, such as antibacterial and anticancer therapies, drug delivery and tissue engineering. In this context, the photothermal conversion efficiency is the most fundamental factor, which requires only a low material concentration, irradiation power and shorter irradiation time. In particular, in the case of GO, the optical absorption is significantly increased due to stable colloidal suspension formation, eventually enhancing its photothermal conversion efficiency [43]. In comparison with others, for instance, Au nanoshells, nanorods, or Au-Ag alloys, graphene has attracted considerable attention because of its stable shape under high laser power, hence, altering their plasmonic resonances and conserving their photothermal conversion efficiency [44]. Furthermore, hydrogels are considered smart polymers because of their specific stimuli-absorbing capacity, including light and alternating magnetic fields, especially light from NIR laser, to generate and control local heating [45]. Nevertheless, hydrogels can easily alter their reversible structure upon variations in local conditions, such as temperature or pH [46]. To overcome these issues, immobilizing GO nanosheets is the most effective way to not only ameliorate the mechanical properties of the hydrogel, but also accomplish NIR light responsiveness; thus, it has been extensively investigated for biomedical applications [47][48][49]. Benefiting from the excellent photothermal properties of GO and the mechanical properties of hydrogel, GGels also exhibit high photothermal conversion efficiency that converting NIR light into heat and optimal mechanical properties for their promising potential in different photothermal-based biomedical applications.
Currently, heating is widely used as an effective and useful method for cancer therapy due to the burning of cancerous cells and tumors upon the enhancement of biological molecular temperature. Additionally, for non-superficial treatments, irradiation by laser at NIR was extensively investigated to minimize damage to non-specific surrounding tissues [80] . Among the promising photothermal materials, graphene-incorporated materials have attracted much attention because of their outstanding properties, especially the high absorption of NIR. Therefore, graphene/derivative graphene-based materials have been employed in diverse applications, such as antibacterial and anticancer therapies, drug delivery and tissue engineering. In this context, the photothermal conversion efficiency is the most fundamental factor, which requires only a low material concentration, irradiation power and shorter irradiation time. In particular, in the case of GO, the optical absorption is significantly increased due to stable colloidal suspension formation, eventually enhancing its photothermal conversion efficiency [81]. In comparison with others, for instance, Au nanoshells, nanorods, or Au-Ag alloys, graphene has attracted considerable attention because of its stable shape under high laser power, hence, altering their plasmonic resonances and conserving their photothermal conversion efficiency [82]. Furthermore, hydrogels are considered smart polymers because of their specific stimuli-absorbing capacity, including light and alternating magnetic fields, especially light from NIR laser, to generate and control local heating [83]. Nevertheless, hydrogels can easily alter their reversible structure upon variations in local conditions, such as temperature or pH [84]. To overcome these issues, immobilizing GO nanosheets is the most effective way to not only ameliorate the mechanical properties of the hydrogel, but also accomplish NIR light responsiveness; thus, it has been extensively investigated for biomedical applications [85,86,87]. Benefiting from the excellent photothermal properties of GO and the mechanical properties of hydrogel, GGels also exhibit high photothermal conversion efficiency that converting NIR light into heat and optimal mechanical properties for their promising potential in different photothermal-based biomedical applications.
3.
Photothermal-Based Biomedical Applications of GGels
There are many exceptional advantages of photothermal-sensitive GGels in the field of biomedical applications, including NIR-mediated hyperthermic anticancer therapy, NIR-triggered drug release system, antimicrobial and wound healing, tissue engineering and bone regeneration, owing to their fascinating properties such as cost-effectiveness, straightforward functionalization and high photothermal conversion efficiency. GGels could act as innovative materials exhibiting significant potential in biomedical applications
