Effects of Photodynamic Therapy with Redaporfin on Tumor Oxygenation and Blood Flow in a Lung Cancer Mouse Model

Abstract

Three photodynamic therapy (PDT) protocols with 15 min, 3 h and 72 h drug-to-light time intervals (DLIs) were performed using a bacteriochlorin named redaporfin, as a photosensitizer. Blood flow and pO 2 changes after applying these protocols were investigated in a Lewis lung carcinoma (LLC) mouse model and correlated with long-term tumor responses. In addition, cellular uptake, cytotoxicity and photocytotoxicity of redaporfin in LLC cells were evaluated. Our in vitro tests revealed negligible cytotoxicity, significant cellular uptake, generation of singlet oxygen, superoxide ion and hydroxyl radicals in the cells and changes in the mechanism of cell death as a function of the light dose. Results of in vivo studies showed that treatment focused on vascular destruction (V-PDT) leads to a highly effective long-term antineoplastic response mediated by a strong deprivation of blood supply. Tumors in 67% of the LLC bearing mice treated with V-PDT regressed completely and did not reappear for over 1 year. This significant efficacy can be attributed to photosensitizer (PS) properties as well as distribution and accurate control of oxygen level and density of vessels before and after PDT. V-PDT has a greater potential for success than treatment based on longer DLIs as usually applied in clinical practice.

Understanding the glioblastoma tumor biology to optimize photodynamic therapy: From molecular to cellular events

“…Furthermore, Madsen et al demonstrated the ability of Trojan horse cell delivery using immune cells to cross PDT‐opened BBB (Madsen et al., 2013), which remarks that not only high weight molecules can reach brain parenchyma after PDT but also, the opening of tight junctions with formed pores are big enough to lead the passage of cells. Considering that one of the most studied effects of PDT consists of the vascular damage which is achieved by controlling the time interval between PS intravascular injection and illumination, the photoinduced damage of ECs could cause massive destruction that produce vessel collapse and thrombus formation (Karwicka et al., 2019; Lepor, 2008). However, in targeted vascular PDT and with the aim of generating leakage from capillaries, appropriate irradiation dosage must be managed to increase vessel permeability but not induce occlusion; because in this last scenario the arrival of drugs and cells to tumor may be interrupted.…”

Application of photodynamic therapy in complex treatment of purulent diseases of the hand

“…ФДТ -метод лечения онкологических заболеваний, а также некоторых заболеваний кожи (псориаз, ихтиоз, гнойничковые заболевания и др.) или инфекционных заболеваний, воспалительных заболеваний слизистых (в т. ч. хронического пародонтита), основанный на применении фотосенсибилизаторов и лазерного излучения определённой длины волны [10][11][12][13][14][15][16].…”

Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

“…There are three main mechanisms of PDT: the direct killing of cancer cells by photogenerated reactive oxygen species (ROS), tumor-associated vascular damage and activation of anti-tumor immune responses [2,4]. These mechanisms suggest that intricate relations between the nature of the photosensitizer (PS), PS dose, light dose, drug-to-light interval (DLI), the oxygen concentration in the targeted tissue and the mechanism of cell death [2,[5][6][7] are likely to affect the outcome of PDT efficacy.…”

“…In this case, longer drug-to-light intervals (DLI > 12h) are used [8][9][10][11]. At intermediate DLIs (e.g., 3 h) the PS is found mainly in the blood and endothelial cells, with partial accumulation in tumor cells [6,12], and protocols using such intermediate DLIs are designated here as E-PDT.The first step in PDT is the selection of a PS with physicochemical and pharmacological properties adequate for the intended PDT regime [13]. The hydrophilicity/lipophilicity of the PS is one of the most important factors influencing its biological behavior, including uptake by cancer cells, intracellular localization, biodistribution and pharmacokinetics [14,15].…”

“…In this case, longer drug-to-light intervals (DLI > 12h) are used [8][9][10][11]. At intermediate DLIs (e.g., 3 h) the PS is found mainly in the blood and endothelial cells, with partial accumulation in tumor cells [6,12], and protocols using such intermediate DLIs are designated here as E-PDT.…”