The Synthesis Of MoOx@F127 Nanosheets And Its Application For Cancer Therapy

Traditional treatments of cancer mainly include chemotherapy,surgery and radiotherapy.Chemotherapy usually kills tumor cells by using drugs that interfere with cell division.Radiotherapy induced radiation-sensitive cancer cell death by using high-energy rays.It will also damage normal cells when killing cancer ones due to the poor specificity and serious toxic side effects of chemotherapy and radiotherapy.In addition,long-term chemotherapy will also induce drug resistance;surgical treatment is risky,incomplete,and easy to relapse.Therefore,developing a novel treatment modality with high specificity,low toxicity and high efficiency is of great significance for cancer therapy.Photothermal therapy is a new non-invasive treatment for cancer,which uses photo-absorbing agents localized in tumor converting NIR light energy into heat and killing cancer cells via a localized "burning" manner.Compared to normal cells,cancer cells are more sensitive to the heat and can be severely damaged and died soon when the temperature rises to 40?-42°C,leaving the healthy cells unaffected.Various photo-absorbing agents could not only act as photothermal therapeutic agents but also serve as drug carriers.Therefore,the chemo-photothermal combinational therapy of cancer can be achieved by using photothermal therapy agent loaded with antitumor drug,which can enhance the anticancer effect,reduce the dose and side effects of anticancer drug.Based on this,we fabricated a multifunctional nanocomposite(MoOx@F127)with good biocompatibility,efficient photothermal conversion,high drug loading efficiency and pH-dependent degradability.The nanosheets were used as a drug carrier and degradable photothermal agent to provide chemo-photothermal combination cancer therapy both in vitro and in vivo.Single-layer MoOx nanosheets with large size were synthesized by one-pot hydrothermal method,which were then modified with biocompatible F127 after being broken into small fragments via vigorous sonication.Hydrophilic MoOx@F127 nanosheets were finally synthesized,which was confirmed by fourier transform infrared(FTIR)spectra,thermogravimetric analysis(TGA)and atomic force microscopy(AFM).The morphologies and size of the MoOx nanosheets before and after F127 coating were measured using AFM,transmission electron microscopy(TEM).The size and zeta potential distribution of MoOx@F127 were investigated by dynamic light scattering(DLS)measurements.The results showed that MoOx@F127 is single-layer nanosheets with diameters to be about 90 nm,thickness to be about 1.5 nm,zeta potential to be about-14.7 mV and content of F127 to be about 20.79%.MoOx@F127 nanosheets can be uniformly and stability dispersed in various physiological environments.MoOx and MoOx@F127 nanosheets both exhibited strong NIR absorbance,indicating no effect of the surface F1 27 modification.The physicochemical properties of MoOx@F127 were investigated and the results indicated that MoOx@F127 could be an excellent photothermal therapeutic agent for its significant photothermal conversion efficiency,thermal repeatability and thermal stability.In addition,MoOx@F127 nanosheets could avoid in vivo long-term retention and toxicity due to its pH-dependent degradation property.The drug loading efficiency and drug release profile of MoOx@F127 nanosheets were investigated.The drug loading efficiency for DOX was as high as 255.0%(WDOx/WMoOx)and the release profile of drug was in a NIR-sensitive manner.MTT assay was used to evaluate the cytotoxicity of MoOx@F127 and the synergistic antitumor effect of MoOx@F127/DOX on MCF-7 cells.The results demonstrated that MoOx@F127 had no significant cytotoxicity to MCF-7 cells and an outstanding in vitro synergistic anti-cancer effect of the photothermal and chemotherapy combination treatment could be obtained by applying MoOx@F127/DOX.Cellular uptake of free DOX and MoOx@F127/DOX complexes was investigated in MCF-7 cells and evaluated by fluorescence microscopy.The results indicated that MCF-7 cells showed remarkably enhanced cellular uptake of DOX by using MoOx@F127 as nanocarrier and the in vitro intracellular release of DOX exhibited NIR laser-enhanced profile.The results of pharmacokinetics in rats showed that after loading on MoOx@F127,the pharmacokinetic parameters of DOX,such as the area under the drug-time curve,maximum plasma concentration,T1/2 and mean residence time,were all significant improved or prolonged.These results indicated sustained release effect and prolonged blood circulation time of DOX,which can improve the bioavailability of DOX.In addition,the result of in vivo toxicity assessment indicated MoOx@F127 of great biocompatibility.The results of in vivo infrared thermal imaging indicated high photothermal conversion efficiency and efficient tumor-targeted enrichment ability MoOx@F127 or MoOx@F 127/DOX in tumor-bearing mice after i.t.and i.v.injection.Besides,MoOx@F127/DOX distributed in tumor can convert NIR light energy into heat and trigger the release of DOX,which induced“two punch”anti-tumor effects of chemotherapy with photothermal therapy.Taken together,the MoOx@F127 nanosheet reported in the present study showed great potential in biomedical applications because of its good biocompatibility,synergistic anti-tumor effect of chemo-photothermal therapy both in vitro and in vivo and pH-dependent degradation property,which could insure the rapid excretion.