bacteriochlorin and Lung-Neoplasms

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).. 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.. It was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC. 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.

Topics: Animals; Carcinoma, Lewis Lung; Lung Neoplasms; Mice; Photochemotherapy; Photosensitizing Agents

Photodynamic therapy (PDT) with current photosensitisers focuses on local effects and these are limited by light penetration in tissues. We employ a stable near-infrared (NIR) absorbing bacteriochlorin with ca. 8h plasma half-life to increase the depth of the treatment and elicit strong systemic (immune) responses. Primary tumour growth delays and cures of BALB/c and nude mice bearing CT26 mouse colon carcinoma are related to the parameters that control PDT efficacy. The systemic anti-tumour protection elicited by the optimised PDT regimen is assessed by tumour rechallenges and by resistance to the establishment of metastasis after intravenous injection of CT26 cells. The optimised treatment regime offered 86% cure rate in BALB/c mice but no cures in BALB/c nude mice. Cured mice rechallenged over 3 months later with CT26 cells rejected the tumour cells in 67% of the cases. PDT of a subcutaneous CT26 tumour 5days after the additional intravenous injection of CT26 cells very significantly reduced lung metastasis. The PDT regimen optimised for the bacteriochlorin leads to remarkable long-term survival rates, effective immune memory and control of lung metastasis.

Topics: Animals; Carcinoma; Cell Line, Tumor; Colorectal Neoplasms; Female; Immunologic Memory; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Porphyrins; Time Factors; Tumor Burden

Sulfonamides of halogenated bacteriochlorins bearing Cl or F substituents in the ortho positions of the phenyl rings have adequate properties for photodynamic therapy, including strong absorption in the near-infrared (λ(max) ≈ 750 nm, ε ≈ 10(5) M(-1) cm(-1)), controlled photodecomposition, large cellular uptake, intracellular localization in the endoplasmic reticulum, low cytotoxicity, and high phototoxicity against A549 and S91 cells. The roles of type I and type II photochemical processes are assessed by singlet oxygen luminescence and intracellular hydroxyl radical detection. Phototoxicity of halogenated sulfonamide bacteriochlorins does not correlate with singlet oxygen quantum yields and must be mediated both by electron transfer (superoxide ion, hydroxyl radicals) and by energy transfer (singlet oxygen). The photodynamic efficacy is enhanced when cellular death is induced by both singlet oxygen and hydroxyl radicals.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Cell Survival; Energy Transfer; Fluorescence; Humans; Hydroxyl Radical; In Vitro Techniques; Lung Neoplasms; Melanoma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Singlet Oxygen; Tumor Cells, Cultured

Reactive oxygen species generated by photosensitizers are efficacious remedy for tumor eradication. Eleven cycloimide derivatives of bacteriochlorin p (CIBCs) with different N-substituents at the fused imide ring and various substituents replacing the 3-acetyl group were evaluated as photosensitizers with special emphasis on structure-activity relationships. The studied CIBCs absorb light within a tissue transparency window (780-830 nm) and possess high photostability at prolonged light irradiation. The most active derivatives are 300-fold more phototoxic toward HeLa and A549 cells than the clinically used photosensitizer Photogem due to the substituents that improve intracellular accumulation (distribution ratio of 8-13) and provide efficient photoinduced singlet oxygen generation (quantum yields of 0.54-0.57). The substituents predefine selective CIBC targeting to lipid droplets, Golgi apparatus, and lysosomes or provide mixed lipid droplets and Golgi apparatus localization in cancer cells. Lipid droplets and Golgi apparatus are critically sensitive to photoinduced damage. The average lethal dose of CIBC-generated singlet oxygen per volume unit of cell was estimated to be 0.22 mM. Confocal fluorescence analysis of tissue sections of tumor-bearing mice revealed the features of tissue distribution of selected CIBCs and, in particular, their ability to accumulate in tumor nodules and surrounding connective tissues. Considering the short-range action of singlet oxygen, these properties of CIBCs are prerequisite to efficient antitumor photodynamic therapy.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Female; Golgi Apparatus; HeLa Cells; Humans; Lethal Dose 50; Leukemia P388; Lipids; Lung Neoplasms; Lysosomes; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Photochemotherapy; Photosensitizing Agents; Porphyrins; Singlet Oxygen; Tissue Distribution