A Study Of Targeted Photodynamic Therapy For Efficient Killing Of Cancer Stem Like Cells

With the development of modern medicine,cancer treatment has made great progress,but it still faces many problems such as recurrence and metastasis.Studies have shown that this is largely due to the failure to completely eradicate cancer stem cells(CSCs)that sustain cancer growth.For conventional treatment,CSCs produce higher oxidative stress and effective repair of DNA damage through mechanisms such as overexpression of adenosine triphosphate binding cassette drug transporters,upregulation of autophagy pathways,and secretion of anti-apoptotic factors,resulting in enhanced drug resistance.Therefore,there is an urgent need to develop and validate new treatment strategies for CSCs to improve the therapeutic effect of cancers.Photodynamic therapy(PDT)is a form of phototherapy.Depending on the distribution of photosensitizers in the cells and the targeting of organelles(mitochondria,endoplasmic reticulum,lysosomes,etc.),the mechanism of cell death induced by PDT is also different.Aiming at the resistance mechanism of CSCs to cancer therapy,this paper uses two types of photosensitizers that target mitochondria and lysosomes to study the killing of breast cancer stem-like cells(BCSLCs)by PDT.The main contents are as follows:(1)Breast cancer stem-like cells were successfully cultured by serum-free suspension method,and the stem cell identification showed that the cell line has the characteristics of drug efflux of cancer stem cells,which can initiate cancer stem cells as a research object.(2)The mitochondrial targeting photosensitizer PpIX and the lysosomal targeting photosensitizer DTP were applied to CSLCs cell lines,respectively,and their localization in cells was characterized by fluorescence confocal microscopy.Transmission electron microscopy and fluorescence imaging the microstructure and nucleus morphology of cells after PDT injury were studied respectively.It was found that targeted lysosomes have higher PDT killing effect on CSLCs than targeted mitochondria,which may be due to the mitochondrial-dependent lysosomal pathway.(3)The photosensitizers'PpIX and DTP were used to act on three-dimensional tumor stem cell-like spheres,respectively.It was found that DTP-based PDT could effectively inhibit tumor growth,while PpIX-based PDT has no obvious effect.