دانلود رایگان ترجمه مقاله استفاده از سیستم تعلیق اکسید گرافن کاهشی گلوکز برای فتوترمال درمانی سرطان (نشریه RSC 2012)

استفاده از سوسپانسیون اکسید گرافن کاهش یافته توسط گلوکز در فوتوترمال تراپی سرطان

The use of a glucose-reduced graphene oxide suspension for photothermal cancer therapy

A single-step green method for effective reduction and functionalization of graphene oxide (GO) by glucose was developed. Then, efficacy of the glucose-reduced GO sheets in photothermal therapy of LNCaP prostate cancer cells was investigated in vitro. The GO suspension reduced and functionalized by glucose in the presence of Fe catalyst showed a biocompatible property with an excellent near-infrared (NIR) photothermal therapy efficiency better than hydrazine-reduced GO, single-wall and multi-wall carbon nanotube suspensions which even showed some levels of toxicities. For complete destruction of the cancer cells at some time intervals of NIR irradiation (e.g., 0.5 and 12 min with a power density of 7.5 W cm−2), minimum concentrations of the reduced GO sheets (i.e., 1 and 0.05 mg mL−1) were obtained. The high photothermal therapy efficiency and biocompatibility of the glucose-reduced GO sheets were assigned to functionalization of the reduced sheets by gluconate ions which also prevented their aggregation. Our results suggest that the glucose-reduced GO sheets can be used as biocompatible and efficient photothermal agents in upcoming nanotechnology-based cancer therapies without any common functionalization by polyethylene glycol.

1 Introduction

Although valuable techniques (such as surgery, chemotherapy, radiotherapy, and sometimes a combination of them) have been developed in the area of cancer therapies, there are still important obstacles (e.g., severe adverse reactions1,2 and low efficiency versus resistant cancer cells3,4) which should be resolved. In recent years, photothermal nanotherapy has been proposed for effective treatment of advanced-stage cancer, with low side effects.5
7 It relies on heat generation in a nanomaterial upon near-infrared (NIR) photoexcitation and destroying cancer cells by excessive local heating.

Graphene (as a monolayer or a few layers of sp2 -bonded carbon atoms having a honeycomb lattice structure) with unique physicochemical properties (e.g., see ref. 8) has attracted much attention. Furthermore, being very similar to carbon nanotubes (CNTs), graphene is capable of absorbing NIR radiation, because of its delocalized electron arrangement. This absorbed radiation can be given off to vibrational modes of the graphene i.e., transformation into thermal energy, which results in raising the temperature of the cancerous tissue and structural changes in the cellular and protein configurations.9 Hence, graphene sheets with an excellent thermal conductivity10 and a high effective surface area (as the thinnest sheet) can be considered as one of the most effective nanomaterials in photothermal nanotherapy applications.

So far, only a few works about photothermal therapy of cancer cells by graphene-based nanomaterials have been reported. For example, for the first time, Yang et al.11 studied photothermal therapy of cancer cells in vivo, by using nanoscale graphene oxide (nGO) sheets coated by polyethylene glycol (PEG). Then, the effect of surface chemistry and size of nanoscale graphene oxide sheets on cancer photothermal therapy using ultra-low laser power was reported by this group.12 Robinson et al.13 studied photothermal therapy of cancer cells in vitro, by using a low concentration of nanoscale reduced graphene oxide (nRGO)- PEG. Zhang et al.14 reported the synergistic effect of chemophotothermal therapy using PEGylated graphene oxide. And Markovic et al.15 found that polyvinylpyrrolidone-coated graphene nanoparticles show better performance in photothermal therapy of cancer cells in vitro than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall carbon nanotubes (SWCNTs). In most of these recent works, in order to overcome the water-insolubility of hydrazine-reduced graphene oxide sheets, functionalization by PEG was used. In addition, PEG-functionalized nRGO sheets exhibited a biocompatible property, while nGO and nRGO appeared to show similar levels of toxicity.13

In fact, biocompatibility of graphene-based nanomaterials is one of the most important parameters for their applications in (especially in vivo) photothermal therapy of cancer cells. Although, there are some investigations about biocompatibility of graphene,16 interaction of extremely sharp edges of graphene sheets with cell wall membrane,17 generation of reactive oxygen species by graphene18 and trapping a live cell within the aggregated graphene sheets19 were reported as possible mechanisms for describing the cytotoxicity of graphene sheets. It was also reported that the graphene-based papers can inhibit the growth of bacteria but with a minimal cytotoxicity.20 Cytotoxicity of graphene is also reported to be dose dependent.18,21 Moreover, in the chemical exfoliation method (as one of the most efficient methods for large scale production of graphene), strong reductants such as hydrazine, which is highly toxic, are usually applied for reduction of the synthesized graphene oxide suspensions. Therefore, not only should a biocompatible reductant be selected and used for reduction of the chemically exfoliated GO suspensions (e.g., melatonin,19,22 vitamin C (L-ascorbic acid),23 sugar,24 polyphenols of green tea25 and bacteria26,27), but biocompatibility of the reduced graphene oxide suspension must also be tested for a noninvasive and harmless application of graphene-based nanomaterials in photothermal therapy. In addition, lower amounts and concentrations of graphene with higher NIR absorbance and heat transport efficiencies should be prepared and utilized for the photothermal therapy. One of the ways for achieving this is prevention from aggregation of reduced graphene oxide sheets during the biocompatible reduction process at the neutral pH.

In this work, at first, we used glucose for green reduction and functionalization of graphene oxide sheets synthesized through a chemical exfoliation method. The efficiency of reduction by glucose in the presence of a Fe catalyst was investigated. The biocompatibility of the glucose-reduced graphene oxide was examined and compared to the biocompatibility of hydrazinereduced graphene oxide, without using any PEGylation which is usually applied for functionalization of the reduced sheets. Then, the biocompatible glucose-reduced graphene oxide suspension was used for NIR photothermal therapy of human prostate cancer cells in vitro. For some various NIR irradiation times, the minimum GO concentration required for complete lysis of the cancer cells was obtained. Efficiency and biocompatibility of the graphene-based nanomaterials in photothermal therapy were also compared with those of single-wall carbon nanotubes and multi-wall carbon nanotubes (MWCNTs).