| Thyroid cancer is the most common endocrine system related tumor.Its incidence rate has been rising all over the world in the past decades.The main therapeutic methods are surgical resection,radioactive iodine therapy and postoperative endocrine suppression therapy.Although thyroid cancer has a good prognosis and low mortality,there are still many treatment problems to be solved.For example,some special pathological types with strong invasiveness may be difficult to remove completely,insensitive to radioiodine therapy,and local recurrence of thyroid cancer after operation.In view of the above problems,in addition to the traditional treatment,we need to continue to explore new treatment methods.As a new way of tumor treatment,phototherapy has gradually entered people's field of vision because of its strong selectivity,small side effects and convenient use.Because the anatomical position of thyroid is relatively shallow,phototherapy is more suitable for the treatment of thyroid cancer.The key of phototherapy is the selection of photosensitizers.Among all kinds of photosensitizers,fluoroboron Dipyrrole,as an organic fluorescent dye,has many advantages,such as high fluorescence quantum yield,good photostability and chemical stability,adjustable absorption characteristics and high molar absorption coefficient.Based on the above considerations,we designed and prepared a BODIPY-loaded nanomicelle for photodynamic/photothermal therapy of thyroid cancer.And a BODIPY-loaded nanofibers,which are used for hyperthermic chemotherapy to prevent postoperative recurrence of thyroid cancer.First of all,aiming at the problem of thyroid cancer treatment,this paper designed a kind of nanomicelles based on near-infrared BODIPY.This paper introduces the preparation method,physical and chemical properties of the nanomicelles in detail,and discusses the therapeutic effect and biological safety of the nanomicelles in vivo and in vitro.The specific research contents are as follows.1.The preparation of triphenylamine-iodo-BODIPY nano-micelles(TPA-IBDP NMs)were carried out,and the basic properties of the micelles were characterized.Through transmission electron microscope,particle size analyzer and other technical means,it is verified that the nano-micelles have good good stability,uniform size,and its absorption wavelength is 710 nm.The results of single line oxygen detection and photothermal performance test show that the nanomicelles have good photothermal and photodynamic properties,and have the potential to be the imaging reagents of fluorescence imaging and photoacoustic imaging.2.At the cell level,the endocytosis of the nanomicelles was verified by confocal and flow cytometry.The cytotoxic experiment showed that the nanomicelles had good biocompatibility with cells and could produce good cell killing effect in light.In addition,by flow cytometry,we found that when the concentration of nano-micelles was low,the photodynamic effect was dominant to produce cell killing effect,while with the increase of the concentration,the combined effect of photothermal and photodynamic on cell killing was observed.3.In animal level experiments,this paper verified its good fluorescence imaging function through in vivo and in vitro fluorescence imaging experiments,and highly accumulated in the tumor site with the help of EPR effect of nanoparticles.In the tumor treatment experiment,nanomicelles also showed excellent therapeutic effect.The experimental group was significantly different from other groups,and the biological safety was good.Then,for the recurrence of thyroid cancer,considering that the recurrence of thyroid cancer often occurs in the thyroid bed and neck lymph nodes,local preventive treatment might be more effective than systemic treatment,and has fewer side effects.Nanofibers have the advantages of high drug loading and effective control of drug release.It is often used in the study of postoperative prevention and treatment of local recurrence of tumor,but it has not been used in the study of thyroid cancer.Therefore,we designed a kind of nanofibers containing epirubicin hydrochloride(EPI)and triphenylamine BODIPY(TPA-BODIPY)to prevent local recurrence of thyroid cancer.The specific experiments are as follows.1.In this paper,TPA-BODIPY was synthesized firstly,and its stable and excellent photothermal properties were verified by heating test.At the cellular level,through cytotoxicity experiments,we verified the rationality and effectiveness of thermochemotherapy based on small molecule EPI and BODIPY in synergistic treatment of thyroid cancer cells.2.EPI and BODIPY co-loaded polylactic acid/polyethylene oxide nanofibers was prepared by electrospinning.The drug content,heating performance,fluorescence performance,in vivo distribution and release of chemotherapeutic drugs were tested.The results show that this kind of nanofibers can realize the local thermochemotherapy of precise wound location after thyroid cancer surgery.In animal experiments,no tumor recurrence was found in the implanted nanofibers with light group,which showed a good inhibitory effect on recurrence and good biological safety.The prepared nanofibers do not need to be taken out,and can be naturally degraded in vivo,and can exist in vivo for a period of time,which is convenient for repeated light therapy.In this paper,following the principle of simple,practical and convenient clinical transformation,we designed two different BODIPY based phototherapeutic nano formulations to explore the treatment of thyroid cancer from different angles.As a supplement to the traditional therapy,it provides a new idea for the treatment of thyroid cancer. |
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