Photodynamic therapy of lung cancer with photosensitizers based on polycationic derivatives of synthetic bacteriochlorin (experimental study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). METHODS: The anticancer efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma were studied in vitro and in vivo. RESULTS: It was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC50 values were about 0.8 µM for tetracationic PS and 0.5 µM for octacationic PS. In vivo studies have shown that these PS provide effective inhibition of the tumor growth with an increase in the lifespan of mice in the group by more than 130%, and more than 50% survival of mice in the group. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high photodynamic efficacy caused by the induction of necrosis and apoptosis of cancer cells, including cancer stem cells, and a sharp decrease of mitotic and proliferative activity. Studied polycationic photosensitizers are much more effective at destroying cancer stem cells and newly formed cancer vessels in comparison with anionic photosensitizers, and ensure the cessation of tumor blood flow without hemorrhages and thrombosis.

Antitumor activity of photodynamic therapy with tetracationic derivative of synthetic bacteriochlorin in spheroid culture of liver and colon cancer cells.

Efficient screening of photosensitizers (PS) as well as studying their photodynamic activity, especially PS excited in the near-infrared region, require informative in vitro models to adequately reflect the architecture, thickness, and intercellular interactions in tumors. In our study, we used spheroids formed from human colon cancer HCT-116 cells and liver cancer Huh7 cells to assess the phototoxicity of a new PS based on tetracationic derivative of synthetic bacteriochlorin (BC4). We optimized conditions for the irradiation regime based on the kinetics of BC4 accumulation in spheroids and kinetics of spheroid growth. Although PS accumulated more efficiently in HCT-116 cells, characterized by more aggressive growth and high proliferative potential, they were less susceptible to the photodynamic therapy (PDT) compared to the slower growing Huh7 cells. We also showed that 3D models of spheroids were less sensitive to BC4 than conventional 2D cultures with relatively identical kinetics of drug accumulation. Our findings suggest that BC4 is a perspective agent for photodynamic therapy against cancer cells.

On the mechanisms of photodynamic action of photosensitizers based on polycationic derivatives of synthetic bacteriochlorin against human lung cancer cells A549 (in vitro study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin. METHODS: The efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods. RESULTS: It was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 µM for tetracationic PS and 0.57 µM for octacationic PS under irradiation at 30 J/cm2 while in the "dark" control they were higher than 100 µM for both PSs. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity.

Primary Undifferentiated Pericardial Sarcoma after Radiоtherapy for Hodgkin Lymphoma.

Various types of sarcomas arise as a result of postradiation chronic fibrous pericarditis. A primary undifferentiated spindle cell pericardial sarcoma is a rare type of sarcoma after radiotherapy. The risk of sarcoma increases with time after treatment of cancer. A 55-year-old woman underwent successful radiation and chemotherapy for Hodgkin lymphoma 20 years ago. She was hospitalized with typical manifestations of severe heart failure. Echocardiography, сomputed tomography of the chest and magnetic resonance imaging scan of the heart detected neoplastic formations of the pericardium. A biopsy of the pericardium was performed. Histological, immunohistochemical, and genetic studies showed a primary undifferentiated spindle cell pericardial sarcoma (an extremely rare type of sarcoma).