Photosensitizers driven by mesenchymal stem cells for precise photodynamic therapy of cancer

According to a report from the National Cancer Institute (NCI), in 2018 alone, nearly 1.74 million people in the United States will be diagnosed with cancer, and about 600000 of them will die of cancer Cancer statistics released by China National Cancer Center this year also show that cancer has become the first killer of human beings At present, the treatment methods for cancer mainly include surgery, radiotherapy, chemotherapy and targeted therapy Although these therapies have certain effects on cancer, the surgical trauma is large, and the side effects of radiotherapy and chemotherapy are serious While the side effects of targeted therapy are small, but the expensive targeted drugs are not suitable for all cancer patients Therefore, it is of great practical significance to develop more efficient and cheap cancer treatment methods Fig 1 Schematic diagram of cancer photodynamic therapy with mesenchymal stem cells as carriers (photo source: biomaterials) Recently, juyoung Yoon of Lihua women's University in South Korea and Ki sung Hong and hyung min Chung of Jianguo University in South Korea jointly reported a photosensitizer transport scheme that can be used for precise photodynamic tumor treatment Photodynamic therapy (PDT) is a new method for the treatment of tumor diseases Compared with the traditional treatment, this method is less invasive, more targeted and less toxic However, how to effectively transport photosensitizers (PCS) to the lesions is the biggest problem that PDT needs to solve Using mesenchymal stem cells (MSCs) as carriers, the team successfully transferred photosensitizers to human colon cancer cells (HCT116) to achieve accurate photodynamic therapy This achievement was published in biomaterials (DOI: 10.1016 / j.biomaterials 2018.09.041) under the title of "sensitive stemcell driven active photosensors for precision photodynamic oncotherapy" Fig 2 Synthesis route of photosensitizer (photo source: biomedicals) the first and most important step of photodynamic therapy is the design and synthesis of photosensitizer The author selected phthalocyanine dye containing zinc as the parent of photosensitizer, because the parent of this dye can produce singlet oxygen efficiently after absorbing 650-800 nm light The author plans to use sodium benzenesulfonate to modify the dye matrix On the one hand, this modification is to improve the solubility of photosensitizer, on the other hand, it provides the possibility for the assembly of photosensitizer, and on the other hand, this amphiphilic structure is more conducive to the penetration of photosensitizer through cell membrane After the complete design, the synthesis of photosensitizer is relatively simple The sodium benzenesulfonate substituted phthalonitrile is obtained by the reaction of nitrophthalonitrile and sodium p-hydroxybenzenesulfonate, and the photosensitizer can be obtained by the reaction of unmodified phthalonitrile and zinc acetate (Fig 2) Fig 3 A) UV absorption spectra of photosensitizers at different fetal bovine serum concentrations; b) fluorescence emission spectra of photosensitizers at different fetal bovine serum concentrations; c) singlet oxygen production capacity of photosensitizers without fetal bovine serum; d) singlet oxygen production capacity of photosensitizers in the presence of 1% fetal bovine serum (photo source: biomaterials) In accordance with the design, photosensitizers will gather in water, showing extremely weak fluorescence signal and singlet oxygen production capacity (Fig 3a, B, c) Once combined with protein rich fetal bovine serum, the fluorescence and singlet oxygen production capacity will be restored (Fig 3D) After understanding the characteristics of photosensitizers, the author began to study photodynamic therapy First of all, the author must make sure that the photosensitizer can be transported to the designated site by using mesenchymal stem cells They inject the mesenchymal stem cells (MSc PCs) containing photosensitizers into the vicinity of cancer cells by injection, and then use in vivo fluorescence imaging to monitor the location of cancer cells and photosensitizers in mice in real time It was found that after a period of injection, most of the photosensitizers gathered in the cancer cells, while the direct injection of photosensitizers had no similar effect (Figure 4a), indicating that mesenchymal stem cells played a decisive role in the transport of photosensitizers After that, the author began to investigate the effect of photodynamic therapy The results showed that the tumor growth was effectively inhibited after 5 days of laser irradiation at 655 nm (Fig 4b) Fig 4 A) in vivo imaging contrast of mice injected with MSC PCs and PCs; b) tumor volume after 5 days of light (photo source: biomaterials) Full text highlights: the author creatively uses mesenchymal stem cells as a transport carrier to achieve accurate transport of photosensitizers Authors: xingshuli, c-yoon Kim, Jeong min shin, Dayang Lee, gyungmi Kim, hyung min Chung, Ki sung Hong, juyoung Yoon