| BackgroundCancer has become the main cause of the death worldwide, which has overtakenheart-related disease. Various clinical cancer therapies including surgery, radiotherapy, andchemotherapy have been developed to ablate cancer cells. However, the above approaches areusually limited by the risks of killing normal tissues, an increased incidence of tumormetastasis, and destroying the immune system. As a promising alternative to conventionalsurgery and other therapies, near-infrared (NIR) laser-induced photothermal therapy (PTT)has emerged as an appealing therapeutic strategy for cancer treatment. By using heatgenerated from absorbed NIR light energy, PTT can kill cancer cells via a localized “burning”manner. As a result, PTT can availably avoid the risks mentioned above with the minimalinvasiveness and high selectivity. In addition, this technique also exhibits several otheradvantages over traditional approaches, such as simpler procedure, fewer complications, andshorter period in hospital.Currently, noble metal-based nanostructures, Cu-based semiconductor nanoparticles,carbon-based nanomaterials, as well as organic polymers and assembly have been wellprepared as powerful PTT agents to kill cancer cells both in vitro and in vivo.Althoughpromising, these agents cannot achieve the essential clinical implementation due to theirunknown long-term toxicity. For example, carbon-based nanotubes and graphene are highlystable under various physiological conditions and can induce oxidative stress and pulmonaryinflammation. Moreover, metallic nanomaterials are poorly metabolized and have potentialtoxicity against normal tissues and organs. To effectively avoid serious adverse effect causedby unknown long-term toxicity and benefit the practical application in clinic, it is highlyimportant to develop PTT agents with admirable biocompatibility and low systemic toxicity.As an important family of multifunctional materials, magnetic nanoparticles have beenadopted in a wide range of bio-related fields such as magnetic resonance imaging (MRI),targeted drug delivery, cancer treatment, as well as biomolecule separation. One excellentexample is that superparamagnetic nanoparticles based on Fe3O4have been approved ashigh-performance contrast agents in MRI by Food and Drug Administration (FDA), whichindicating the long-term safety of these kinds of nanomaterials and their potential usages inbiomedicine. Recent studies have demonstrated the design and construction of magneticnanocomposites and their photothermal effect against bacteria and cancer cells. However, these systems only focused on the final results of PTT instead of detailed studies includingsystemic cytotoxicity of nanoagents and induced photothermal toxicity under differenttreatments. More importantly, PTT against C6cells have not been studied till now, revealingmore potential for glioma treatment along with the cerebral tumor operation.Inspired by these,here we present a novel PTT agent based on PEGylated Fe3O4nanoparticles(PEG-Fe3O4) forin vitro cancer treatment of C6cells.Magnetic nanoparticles were synthesized via a facile one-pot solvothermal route at first.PEG molecules coated on the surface of PEG-Fe3O4endowed these nanomaterials with greatdispersibility and dissolvability in various physiological conditions. Results of MTT assaysindicated the low systemic cytotoxicity of PEG-Fe3O4. When incubated with the NIR laseractivated PTT agents, the viabilities of C6cells were suppressed step by step with theincreasing of agent concentration and irradiation period. Last but not least, visual microscopeimages based different staining methods further demonstrated the unexceptionablephotothermal anti-cancer efficacy of our PEG-Fe3O4upon NIR laser irradiation with a lowlaser power density and a short irradiation period.PurposeFinding an effective method for the treatment of gliomaMethodsFirst, preparation of PEG-Fe3O4.Nanoparticles were fabricated via one-pot solvothermalmethod and C6cells culture.Second,testing cytotoxicity of PEG-Fe3O4incubated with C6cell by MTT assays.Third, solution containing PEG-Fe3O4with different concentrations was exposed to an808nm laser upon different treatment periods.In order to test the properties ofphotothermal agents.Fourth, want to know the photothermal toxicity of PEG-Fe3O4, with and without PEG-Fe3O4, these cells were exposed to an808nm laser with an intensity of2W·cm-2for5min, respectively. C6cells were then incubated at37℃with5%CO2for another24h.After treatment, these samples were treated with MTT.ResultsFirst, the synthetic PEG-Fe3O4were detected by TEM、SEM、XRD、SAED。The successful modification of PEG molecules on surface of PEG-Fe3O4couldextremely enhance the dissolvability and colloidal stability of these nanoparticles insimulated body fluid (SBF) as expected.Second, viabilities of Hela cells and C6cells were not hindered by PEG–Fe3O4up to aconcentration of1mg·mL1, herein revealing the significantly low cytotoxicity ofour magnetic nanoparticles. Moreover, we also investigated the behavior ofPEG-Fe3O4in living cells via observing the morphological changes. Afterco-incubation with PEG-Fe3O4, inverted microscopy images exhibited that all theC6cells spread and proliferated equally n both the control and test groups.Third, temperatures of all the PEG-Fe3O4samples increased with the irradiationperiods,and the temperature increased more rapidly with increasing theconcentrations of PEG-Fe3O4.The temperature of solution containing PEG-Fe3O4with a concentration of1.0mg·mL-1was enhanced by23.8℃after NIR laserirradiation.In contrast,the temperature of pure water was only increased by3.8℃.So,PEG-Fe3O4has excellent ability of photothermal conversion.Fourth, after24h of incubation with increasing concentration of PEG-Fe3O4neither the cellviability nor the proliferation of C6cells was extremely hindered by the presence ofthese photothermal agents. However,the NIR laser irradiation could not result in thedeath of cells, indicatin the negligible toxicity induced by NIR light with the presentirradiation intensity period.Moreover,these findings clearly described that the deathof C6cells was mainly caused by the photothermal effect of PEG-Fe3O4.ConclusionsPEG-Fe3O4has the potential to be an effective agent for phototthermal therapy. |
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