Activity Evaluation Of Lysosomal Targeted Phthalocyanine

Lysosomes are cellular "waste metabolism in plants". Recent studies indicated that the lysosomal targeting photosensitizers always have good safety and excellent photosensitive anticancer activity. The microenvironment of lysosome is acidic. So,polyamine structure modified drugs tend to gather in the lysosomes of cells. According to this theory, our resaerch group preliminary design and synthesis 8 polyamines modified zinc phthalocyanine. In this paper, the subcellular localization, endocytosis and photosensitivity and antitumor activity of these zinc phthalocyanine were studied.The relationship between the structure of polyamine phthalocyanine and the activity of photosensitivity and antitumor activity was sought, which could provide a valuable reference for the design of phthalocyanine with good photosensitivity. To promote the phthalocyanine photosensitizer in the field of photodynamic therapy in the clinical application process, with a view to the phthalocyanine photosensitizer design and help to help, the main research results are as follows.1. The subcellular localization of eight phthalocyanines in human non-small cell lung cancer cells (A549) was detected by laser confocal microscopy and organelle-specific fluorescent probes. The results showed that eight polyamines phthalocyanine were located in lysosomal organelles.2. The cell uptake rate and endocytosis of 8 phthalocyanines were studied by UV spectrophotometry and four kinds of endocytosis inhibitors. The results show that the phthalocyanine is an energy-dependent process in the process of ingestion. The molecules involved in endocytosis play a role in multiple endocytosis routes. The morphology of phthalocyanine will affect the uptake pathway.3. The effect of phthalocyanine on the proliferation of tumor cells was studied by MTT colorimetry. The results showed that the phthalocyanine had low toxicity to A549 cells, indicating its excellent safety. On the contrary, after irradiation by light, all of phthalocyanine showed satisfied antitumor activity.4. The ability of intracellular reactive oxygen production of eight phthalocyanine photosensitization reactions was studied by fluorescence probe method. Octa-substituted polyamines phthalocyanine and its ability to produce more reactive oxygen species than tetra-substituted polyamine phthalocyanines.