Conjugated Polymer/Glucose Oxidase-based Nanomaterials For Antitumor Research

Cancer has become the main reason that lead to human death in the world.Therefore,the development of novel multifunctional antitumor materials has attracted extensive attention of researchers.Photothermal therapy（PTT）is an advanced antitumor method that usually kill tumor cells by the heat generated under the stimulation of near-infrared（NIR）light by enriching photosensitizers in the body or lesions.Conjugated polymer nanoparticles（CPNs）have been widely used in the biomedical field because of their excellent optical properties,good biocompatibility and stability.However,the overexpression of heat shock protein（HSP70）can cause the thermotolerance of tumor cells and decrease the effect of PTT.This paper focuses on the surface modification of CPNs,prepared and characterized the functionalized conjugated polymer nanoparticles（CPNs-G）.Under the mediation of CPNs,the activity of glucose oxidase（GOx）was regulated by NIR light,which improved the effect of photothermal therapy and achieved the synergistic effect of starvation/photothermal to kill tumor cells.The main research contents are as follows:1.Functionalized conjugated polymer nanoparticles（CPNs-G）were prepared by assembling conjugated polymer（PDPP）and amphiphilic molecule(DSPE-PEG₂₀₀₀-COOH)and modifying GOx on its surface,which owns high photothermal conversion efficiency and glucose catalytic ability.The structure of CPNs-G was characterized by Fourier transform infrared spectroscopy（FTIR）,ultraviolet-visible absorption spectroscopy（UV-vis）,transmission electron microscopy（TEM）,dynamic light scattering experiments（DLS）.Moreover,the photothermal conversion efficiency of CPNs-G was calculated to be as high as 58.1%by photothermal conversion experiments.Under the irradiation of NIR light,PDPP can convert light into heat and rapidly increase the surrounding temperature,thereby accelerating the catalytic reaction of GOx.Compared with CPNs,CPNs-G has high glucose catalytic ability,which overcomes the singleness of CPNs and expands the application of conjugated polymer nanoparticles in the biological field.2.The killing ability and mechanism of CPNs and CPNs-G on tumor cells were explored,and it was found that photothermal/starvation therapy can synergistically improve the killing effect of nanoparticles on tumor cells.MTT results showed that 76.5%of tumor cells were destroyed by the photothermal/starvation synergistic treatment of CPNs-G.The mechanism of CPNs-G for anti-tumor research was analyzed by measuring reactive oxygen species（ROS）,mitochondrial membrane potential（JC-1）,adenosine triphosphate（ATP）,heat shock protein（HSP）.The study found that under NIR light irradiation,the expression of HSP70 in CPNs-G treated cells was reduced by 19%,compared with CPNs treated cells.Therefore,CPNs-G can consume glucose in tumor cells through the NIR light-regulated enzyme-mediated starvation effect,inhibit the expression of heat shock protein（HSP70）,thus improving the effect of PTT.Compared with traditional photothermal therapy（PTT）,CPNs-G can affect the normal metabolism of tumor cells through GOx starvation therapy,which not only improves the therapeutic effect of PTT,but also realizes the synergistic effect of PTT therapy and starvation therapy,avoiding the biotoxicity caused by loading enzyme with inorganic photothermal reagents in the past.