ROS-responsive Nanocarrier Combined Photodynamic With Chemotherapy For Thyroid Cancer Therapy

Background and object:Thyroid carcinoma is the most common malignant tumor in the endocrine system.In recent years,the incidence of thyroid cancer has been increasing.In the United States,the incidence of thyroid cancer has increased by an average annual increase of6.4%over the past 10 years,while the prevalence of thyroid cancer has risen to third in female malignant tumors.Patients with DTC have a long disease-free survival and a good prognosis,but in some patients it is still impossible to avoid recurrence or distant metastasis.According to statistics,about 20%patients with thyroid cancer have recurrence or cervical lymph node metastasis or distant metastasis within ten years after operation.In addition,some refractory thyroid cancers,including medullary thyroid carcinoma,undifferentiated thyroid carcinoma and partially iodine resistant differentiated thyroid carcinoma,have an average survival time of only 0.5 to5 years.We urgently need to find a more effective treatment for refractory thyroid cancer to improve survival.Photodynamic therapeutic therapy?PDT?is a kind of photo-excited chemical therapy.Photosensitizer absorbs the energy of photons and transitions to the excited state.The excited photosensitizer agent transfers the energy to oxygen,producing singlet oxygen,superoxide radical,and many reactive oxygen specieses?Ros?.Ros can react with nearby biomolecules to produce cytotoxicity and kill tumor cells.It has become a new method with great potential for the treatment of advanced tumors.The effect of light absorption is good,which makes pdt feasible in the treatment of thyroid carcinoma.In this study,we designed and synthesized ros responsive hyperbranched polymer,and prepared high efficient drug carriers carrying photosensitizer?Ce6?and Solafenide?Sfb?for the treatment of refractory thyroid carcinoma.This carrier can not only be enriched in tumor tissue,but also be used in the treatment of refractory thyroid carcinoma.It can also increase the level of ros in tumor tissue under 660nm laser irradiation,rapidly disintegrate the nano-carrier in tumor tissue and release the chemotherapy drug quickly,so as to enhance the anti-tumor effect,reduce the dosage of chemotherapeutic drugs,and reduce its side effects.Methods:1.We measured the particle size and potential by the particle size analyzer and of the nanoparticles observed the morphology by scanning electron microscope.2.the distribution of drugs was detected by laser confocal microscopy and flow cytometry after co culture of nanoparticles and K1 cells.3.the activity of different concentrations of nanoparticles and K1 cells after different power laser treatment were detected by enzyme labeling.4.Balb/c nude K1 tumor bearing mice were injected with fluorescent labeled nanoparticles via tail vein,and nanoparticle distribution was detected by small animal in vivo imaging system.The distribution of nanoparticles in tumor tissues was detected by confocal microscopy.5.Balb/c nude K1 tumor mice were injected with different drug nanoparticles through the tail vein.Then we observed the tumor growth curve.Results:1.The size of ^SfbNPs_Ce6e6 is 158±11.4 nm and the zeta potential is-14.9±2.8 mV,it is spherical structure under electron microscope.2.^SfbNPs_Ce6e6 can enter into K1 cells in vitro.3.^SfbNPs_Ce6e6 can release drug to kill K1 cells with 660 nm irradiating.4.^SfbNPs_Ce6e6 can enter into tumor tissue in vivo.5.^SfbNPs_Ce6e6 can release drug to inhibite the tumor growth with 660 nm irradiating.Conclusion:We designed and synthesized ROS responsive hyperbranched polymer which can load photosensitizer and chemotherapy drugs sorafenib.The nanoparticles which combine photodynamic with chemical therapy can release drugs into tumor and kill thyroid cancer reducing side effects.