Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets
Graphical abstract
Introduction
Photothermal therapy (PTT) utilizes photoresponsive agents taken up by cells and the conversion of absorbed light into local heating to destroy malignant tissue [1]. PTT is considered a minimally invasive cancer treatment approach that is advantageous compared with conventional chemotherapy because its spatial and temporal controllability [2], [3] limit side effects that commonly occur in chemotherapy owing to nonspecific drug delivery to all tissues, including healthy tissues. Multidrug resistance, an additional concern with chemotherapy that leads to treatment failure [4], can also be avoided by PTT because achieving ablative temperatures induces irreversible tissue necrosis [5].
Several types of photoresponsive dyes with maximal absorption peaks in the near-infrared (NIR) region have been explored as imaging agents [6]. Among them, the amphiphilic dye indocyanine green (ICG), is the only NIR imaging agent approved by the U.S. Food and Drug Administration, and used clinically for imaging retinal and choroidal vasculatures, and guiding biopsies [7]. However, the use of ICG suffers dramatically from rapid, light-induced decomposition [8], [9] and clearance, resulting in a plasma half-life of 2–4 min [10]. Thus, various modalities, including calcium phosphosilicate nanoparticles [11], superparamagnetic iron oxide nanoparticles [12], gold nanoparticles [13] and polymeric micelles [14], have been utilized to improve the photostability and prolong retention of ICG in the bloodstream.
Carbon-based nanomaterials, such as carbon nanotubes, graphenes and fullerenes, have been intensely investigated for photothermal therapy applications. On a per-mass basis, both carbon nanotubes and graphenes exhibit a larger extinction coefficient of NIR light absorption than gold nanomaterials, and consequently higher photothermal conversion efficiency [15]. Intravenously administered polyethylene glycol-conjugated graphene nanosheets exhibit ultrahigh tumor retention and good photothermal antitumor efficacy [16]. Recently, we demonstrated that the photothermal tumor ablation capacity of poloxamer 407-functionalized graphene nanosheets was superior to that of poloxamer 407-functionalized carbon nanotubes in a murine xenograft tumor model [17]. Although graphene-based nanosheets produce a photothermal effect on their own, reducing the injection dose by loading photoresponsive agents would be desirable from a safety perspective. Moreover, photoresponsive imaging agent-loaded graphene-based nanosheets may be applicable as theranostics for image-guided photothermal therapy.
In this study, we tested whether the loading of photoresponsive imaging agent onto graphene-based nanosheets could provide image-guided and synergistic photothermal anticancer effects. For image-guided photothermal therapy, ICG was loaded onto reduced graphene oxide nanosheets (rGO). To enhance tumor accumulation and image intensity of ICG, we used hyaluronic acid (HA)-modified rGO for ICG delivery.
Section snippets
Synthesis of rGO nanosheets
Graphene oxide (GO) was prepared from graphite powder following a modified Hummer's method [12]. Briefly, graphite powder (0.5 g; Sigma-Aldrich, St. Louis, MO, USA) was added to cold H2SO4 (23 ml). While this mixture was gradually stirred on ice, KMnO4 (3 g) and NaNO3 (0.5 g) were added slowly. The resulting mixture was further stirred for 1 h at 35 °C. Subsequently, 46 ml of triple-distilled water (TDW) was added and the mixture was incubated at 90 °C for 1 h. The reaction was halted by adding 140 ml of
Characterization of ICG/HArGO
ICG was loaded onto the surfaces of rGO or HArGO nanosheets via π–π interaction, as illustrated in Fig. 1A. The loading efficiencies of ICG on rGO and HArGO nanosheets were 100.4% ± 3.6% and 92.3% ± 5.0%, respectively (Fig. 1B). The morphology of ICG/rGO (Fig. 2A) did not differ from that of ICG/HArGO (Fig. 2B). The loading of ICG did not significantly affect the sizes of rGO or HArGO (Fig. 2C). The zeta potential values of nanosheets decreased after loading of ICG onto rGO (Fig. 2D). Immediately
Discussion
Here, we demonstrated that HArGO could substantially increase the photostability and photothermal antitumor potency of ICG. ICG in free form suffers from photo-induced decomposition after NIR laser irradiation. However, by loading onto rGO or HArGO nanosheets, ICG retained its photostability after NIR laser irradiation. Although ICG/rGO and ICG/HArGO showed similar thermal conductivity in vitro, ICG/HArGO showed a greater photothermal effect at the cell level and in tumor-bearing mice by virtue
Conclusions
Our results suggest the potential of ICG/HArGO for image-guided synergistic photothermal antitumor therapy. Loading of the photolabile ICG onto HArGO nanosheets could stabilize ICG upon NIR irradation for photothermal effect. The endogenous photothermal properties of HArGO nanosheets can be exploited to synergistically enhance photothermal activity through loading of photoresponsive imaging agents. In addition, the tumor-specifically activated image intensity of ICG delivered by the HArGO can
Acknowledgments
This work was supported by research grants from the Ministry of Science, ICT and Future Planning (NRF-2015R1A2A1A01005674), and from the Ministry of Trade, Industry & Energy (Technology Innovation Program, grant no. 10050648), Republic of Korea.
References (32)
- et al.
Application of near-infrared dyes for tumor imaging, photothermal, and photodynamic therapies
J. Pharm. Sci.
(2013) - et al.
Degradation kinetics of indocyanine green in aqueous solution
J. Pharm. Sci.
(2003) - et al.
Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography
Surv. Ophthalmol.
(2000) - et al.
Indocyanine green loaded SPIO nanoparticles with phospholipid-PEG coating for dual-modal imaging and photothermal therapy
Biomaterials
(2013) - et al.
Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy
Biomaterials
(2012) - et al.
Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy
Biomaterials
(2013) - et al.
Structure-dependent photothermal anticancer effects of carbon-based photoresponsive nanomaterials
Biomaterials
(2014) - et al.
Cholesteryl hyaluronic acid-coated, reduced graphene oxide nanosheets for anti-cancer drug delivery
Biomaterials
(2013) - et al.
Reduced graphene oxide nanosheets coated with an anti-angiogenic anticancer lowmolecular-weight heparin derivative for delivery of anticancer drugs
J. Control. Release
(2014) - et al.
Graphene and graphene oxide: biofunctionalization and applications in biotechnology
Trends Biotechnol.
(2011)
Safety and tumor tissue accumulation of pegylated graphene oxide nanosheets for co-delivery of anticancer drug and photosensitizer
Biomaterials
Near-infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging
Adv. Mater.
Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia
Int. J. Nanomedicine
Tumor regression in vivo by photothermal therapy based on gold-nanorod-loaded, functional nanocarriers
ACS Nano
Combating the drug resistance of cisplatin using a platinum prodrug based delivery system
Angew. Chem. Int. Ed.
Thermal ablation therapy for focal malignancy
AJR Am. J. Roentgenol.
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These authors equally contributed to this work.