Study On Antitumor Effect Of Functionalized SWCNTs Delivery Carriers Combined With Chemotherapy And PTT

As the most familiar clinical anti-tumor treatment,chemotherapy is usually used to take effects by injection.Taking the DOX·HCl as an example,it has a strong killing effect on breast cancer,gastric cancer,lung cancer and other malignant tumors,but it also has disadvantages such as large toxic and side effects,poor targeting and low bioavailability.In addition,with repeating use of drugs,the tumor can develop drug resistance and reduce the efficacy.In recent years,it has been reported that Photothermal therapy（PTT）was used for anti-tumor therapy,which mainly relied on chemical photosensitizers to transition the ground state to the excited state under the specific wavelengths of light,converting the light energy into the heat energy to achieve the thermal ablation temperature of tumor cells and improving the anti-tumor effect.However,photosensitizers were limited in the applications of biomedicine because of poor stability and easy removal.Based on the above shortcomings of chemotherapy drugs and photosensitizer,some researchers have proposed to modify the nanomaterials with hollow mesoporous structure and solar-thermal conversion effect,coating biocompatible materials on the surface,and loading the chemotherapy drugs and photosensitizer.There was obtained a PTT combined with chemotherapy nanodrug delivery system（NDDS）with reducing drug toxicity、dosage,and improving anti-tumor efficacy.Single-walled carbon nanotubes（SWCNTs）were selected as the research object,which can be seen as a seamless,hollow cylinder formed by graphene oxide（GO）curling around the central axis at a certain spiral Angle.SWCNTs are hollow and long tubular structures with large specific surface area and high functionalization,which can efficiently load drugs inπ-πconjugation mode.However,there are some shortcomings,such as cell toxicity,easy to gather subsidence.Therefore,often with HNO₃,-H₂SO₄ was used as a drug carrier and other strong acid and strong oxidant such as H₂O₂to acidification truncation,then with polyethylene glycol（PEG）,folic acid（FA）and other surfactants on the functional modification,enhance its biocompatibility and targeting of tumor tissue.Using 1-tetracenol（TD）,functionalized SWCNTs were coupled with photosensitizer indocyanine green（ICG）and loaded with the anti-tumor drug DOX,and finally a nano-drug delivery system that could realize chemotherapy and PTT combined with anti-tumor was prepared.The morphology and particle size of SWCNTs composite loading system were evaluated by FT-IR,DSC and XRD,and the modification effects of PEG and FA were investigated.The results showed that the prepared drug loading system of SWCNTs had moderate particle size and good dispersion.The surface of SWCNTs was successfully modified by PEG,FA and other modifiers,and the phase change material 1-tetradecanol（TD）could coat ICG on the surface of SWCNTs.A fast and efficient HPLC method was established for the determination of DOX content,and the scientific rationality of the method was verified.HPLC results showed that the drug loading capacity of SWCNTs was improved after functionalized modification,and the synthesised functionalized drug delivery system had good p H responsive drug release characteristics.Using human breast cancer MCF-7 cells as an in vitro model,fluorescence microscopy and flow cytometry were used to analyze the cell uptake mechanism of SWCNTs loading systems and the combined anti-tumor efficacy of chemotherapy-phototherapy,and to evaluate the anti-tumor efficacy of different modified SWCNTs NDDS under NIR irradiation.The experimental results showed that SWCNT-PEG-FA-ICG/TD@DOX had a strong ability to across the cells.After NIR irradiation,the total apoptotic ratio of MCF-7 cells was increased,and the cell growth cycle was blocked in G0/G1 phase.Meanwhile,PTT combined with chemotherapy in the treatment group induced excessive ROS production.Compared with the blank control group,the anti-tumor effect was improved 5-6times.The functionalized SWCNTs NDDS can significantly improve the anti-tumor effect of DOX while maintaining low dose and toxicity,which has a very broad research prospect and can provide theoretical basis and technical support for the subsequent design and development of novel nanoagents.