Synthesis Of Cyanine Molecular Probes And Their Applications In Optical Imaging And Treatment Of Breast Cancer

Breast cancer is a malignant tumor occurring in the glandular epithelium of the breast,ranking first in the incidence of female cancer in the world.The early prevention,early detection and early treatment of breast cancer can achieve a very high cure rate and survival rate.Fluorescence imaging in the near-infrared region can significantly reduce the scattering of photons within biological tissues,resulting in deeper penetration depth and higher temporal and spatial resolution.Compared with traditional treatment,photothermal therapy kills tumor cells by heating up the light,without damaging surrounding normal tissues,and has advantages such as high tumor targeting and low toxic side effects.The fluorescent molecule of cyanine has good quantum yield and photothermal conversion rate,which can realize fluorescence imaging and photothermal therapy at the same time.In this thesis,organic small molecules were prepared by wrapping organic small molecules into nanoparticles through polymer polyethylene glycol-polylactic acid-hydroxyacetic acid（PEG-PLGA）,and the high permeability and retention effect of solid tumors can effectively promote the aggregation of nanoparticles at tumor sites.This thesis prepares cyanine fluorescent molecules,and conducts fluorescence imaging and photothermal therapy after cell experiments and biosafety experiments.The main research contents are as follows:Firstly,three types of cyanine fluorescent molecular probes were prepared through anhydrous and oxygen-free reactions,and their structures were characterized by mass spectrometry,¹H NMR,¹³C NMR,and infrared spectrum.At the same time,the UV absorption spectrum and fluorescence spectrum of three types of cyanine fluorescent molecular probes were measured.The results showed that the emission range of the three probes ranged from the visible light region to the near-infrared region,and they had non peak fluorescence emission in the Second Near-Infrared Window,enabling NIR fluorescence imaging.Among the three fluorescent molecular probes,me-IR-825 exhibits better emission performance in the near-infrared region.Considering the water solubility of organic small molecules,they were prepared as PPIR nanoprobes with good dispersibility and a diameter size of about 100 nm.Secondly,the photothermal performance of three types of cyanine fluorescent molecular probes was tested.After irradiation with an 808 nm laser,all three types of cyanine fluorescent molecular probes showed photothermal heating effect,with the fluorescence molecular probe me-IR-825 showing the best heating effect.Finally,the fluorescent molecular probe was selected for the next step of cell and animal experiments.Human breast cancer cell lines MCF-7 and MDA-MB-231 were selected for cytotoxicity test.In vitro cell experiments showed that the fluorescent molecular probe me-IR-825 had good biocompatibility to the two kinds of cells.The photothermal therapy experiment was conducted on MCF-7 cells,and the results showed that the fluorescent molecular probe me-IR-825 could effectively heat up and kill tumor cells under the irradiation of an 808 nm laser.Finally,the fluorescent molecular probe me-IR-825 has passed in vivo biosafety testing.At the level of living small animals,compare the NIR-II fluorescence imaging and photothermal therapy effects of free fluorescent molecular probe me-IR-825 and prepared PPIR nanoprobes.The results indicate that compared to a single organic small molecule,the nanoprobe has better tumor targeting in tumor bearing mice.At the same time,photothermal therapy experiments have confirmed that the fluorescent molecular probe me-IR-825 and PPIR nanoprobes have certain therapeutic effects on tumors.There are 56 figures,3 tables and 129 references in this thesis.