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Antimicrobial photodynamic therapy (aPDT) is an alternative to antibiotics that has potential for the treatment of chronic skin wounds, but requires improved, highly selective photosensitizer systems. Rhenium (Re)‐complex‐ and iridium (Ir)‐complex‐based phospholipid conjugates, as PDT‐functional building blocks for liposomes, are presented, and varying structural components and proportion of compounds are explored, including adjusting the cholesterol and polyethylene glycol (PEG)‐lipid contents, incorporating ethylenediaminetetraacetic acid (EDTA)‐lipid, and introducing the cationic lipid 1,2‐dioleoyl‐3‐trimethylammonium propane (DOTAP) to enhance their efficacy and selectivity in aPDT. Ir/Re‐liposomes have nanostructurally enhanced photoactivity compared to monomeric Ir/Re‐lipids. Ir‐liposomes exhibit stronger light absorption and higher emission generation (>threefold) than Re‐liposomes, resulting in superior efficacy against Staphylococcus aureus while maintaining better tolerability toward host cells. Formulations with higher cholesterol (40 mol%) and PEG‐lipid (5%) content demonstrate increased potency against S. aureus. The incorporation of EDTA‐lipid significantly enhances aPDT efficacy but also increases toxicity toward host cells. Incorporation of DOTAP alters the nanoparticles' surface charge, potentially improving their interaction with bacterial walls, but negatively impacts their stability, leading to aggregation of the nanoparticles. Ir‐HC demonstrates ideal characteristics (effectiveness, selectivity, and stability) for aPDT under the tested conditions, indicating the importance of the structural design of Re‐ and Ir‐complex liposomes for their selectivity in aPDT. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a well-described technique that is primarily used for thin and superficial tumors. Despite the advantages of immune response upregulation, high complete response rates and excellent cosmetics and preservation of tissue structure, the limited light penetration into tissue complicates achieving full-thickness/large-volume treatment of pigmented, thicker, deep-seated or diffuse metastatic tumors1. Reported in vitro studies in melanoma and breast cancer cells show increased expression of major histocompatibility complex I after the combination of psoralen and X-radiation, which is representative of a potential immune response upregulation2. The aim here is to investigate the clinical photosensitizer Verteporfin (VP) as a radiosensitizer to achieve deep tissue penetration while retaining immune upregulation, and thereby enhance tumor-specific radiation responses in pancreatic cancer3 and melanoma4, which are aggressive tumors with high metastatic potential and low survival rates. In vitro studies were carried out with bioluminescent human pancreatic cancer (Panc-1-Luc-2) and murine melanotic melanoma (B16F10) cell lines. The cells were irradiated using 225 kVp (XRAD) or 6 MeV (Linac) X-ray beams, and the treatment response was measured by clonogenicity. In all cases, the presence of VP in the cells reduced survival compared with X-ray only controls: e.g. the group irradiated in the Linac, which includes a contribution from VP activation by X-ray induced Cherenkov light, reached up to 5 Logs of cell death after a single fraction of 10 Gy. In the ex-ovo model, duck eggs at 8 days post fertilization were engrafted with 15 µL (∼5 × 107) of Panc-1-Luc-2 or B16F10-Luc cells. Treatment was given 3 days later using topical VP administration with irradiation 1.5 h later. Combining a single fraction of 5 Gy with 5 µg/mL VP gave >2-fold reduction of the bioluminescence compared to <1 fold for radiation alone. After 3 daily fractions, the in ovo tumors treated with VP + radiation showed undetectable bioluminescence signal until sacrificed at 2 d after the last fraction. These studies are intended primarily to generate baseline response data for radiodynamic therapy with different nanoparticle formulations, including both lipid-porphyrin porphysomes and metal nanoclusters. ACKNOWLEDGEMENTS This work is supported by the Canadian Institutes of Health Research, The Terry Fox research institute and a Tri-Council NRFR grant. L. Pires is supported by the Banting Fellowship. [ABSTRACT FROM AUTHOR]

This study aimed to assess the photodynamic effect of Phonozen, a newly developed photosensitizer, on varied illumination wavelength of 405 nm and 664 nm in a mouse model with peritoneal carcinomatosis. Peritoneal carcinomatosis was induced by IP injection of 1 × 106 MKN45-luc cells to 9 week old female athymic nude mice. Ten days after induction, PDT was performed on 60 mice injecting Phonozen 3 hours before PDT. Twenty mice for each group underwent intra-peritoneal catheterization and underwent (A)no irradiation, irradiation with (B) 405nm, and (C) 664 nm for 1hour, delivering 50J per mouse. Fifteen of each group were observed for 20 weeks for survival analysis and five of each group were sacrificed 2 days after for quantitative assessment of necrosis status. Both irradiation approach with 405 nm and 664 nm significantly prolonged the survival of PC mice over control group. No survival difference were observed between two irradiated group. Semiquantitative assessment showed significantly higher proportion of responder following irradiation of 405 nm than 664 nm. Phonozen shows effective photodynamic tumoricidal effect. Activated by same power, 405 nm is more effective than 664nm for treatment of PC mice model [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with significant risk of fatality. Due to its pigmentation, light-based imaging and treatment techniques are limited to near the tumor surface, which is inadequate, for example, to evaluate the microvascular density that is associated with prognosis. White-light diffuse reflectance spectroscopy (DRS) and near-infrared optical coherence tomography (OCT) were used to evaluate the effect of a topically applied optical clearing agent (OCA) in melanoma in vivo and to image the microvascular network. DRS was performed using a contact fiber optic probe in the range from 450 to 650 nm. OCT imaging was performed using a swept-source system at 1310 nm. The OCT image data were processed using speckle variance and depth-encoded algorithms. Diffuse reflectance signals decreased with clearing, dropping by ∼90% after 45 min. OCT was able to image the microvasculature in the pigmented melanoma tissue with good spatial resolution up to a depth of ∼300 μm without the use of OCA; improved contrast resolution was achieved with optical clearing to a depth of ∼750 μm in tumor. These findings are relevant to potential clinical applications in melanoma, such as assessing prognosis and treatment responses. Optical clearing may also facilitate the use of light-based treatments such as photodynamic therapy. [ABSTRACT FROM AUTHOR]

Pythiosis is an infectious disease caused by Pythium insidiosum, a fungus-like organism. Due to the lack of ergosterol on its cell membrane, antibiotic therapy is ineffective. The conventional treatment is surgery, but lesion recurrence is frequent, requiring several resections or limb amputation. Photodynamic therapy uses photo-activation of drugs and has the potential to be an attractive alternative option. The in vitro PDT response on the growing of Pythium insidiosum culture was investigated using three distinct photosensitizers: methylene blue, Photogem, and Photodithazine. The photosensitizer distribution in cell structures and the PDT response for incubation times of 30, 60, and 120 minutes were evaluated. Methylene blue did not penetrate in the pathogen's cell and consequently there was no PDT inactivation. Photogem showed heterogenous distribution in the hyphal structure with small concentration inside the cells. Porphyrin-PDT response was heterogenous, death and live cells were observed in the treated culture. After 48 hours, hyphae regrowth was observed. Photodithazine showed more homogenous distribution inside the cell and with the specific intracellular localization dependent on incubation time. Photodithazine first accumulates in intracellular vacuoles, and at incubation times of one hour, it is located at all cell membranes. Higher inhibition of the growing rates was achieved with Photodithazine -PDT, over 98%. Our results showed that the photosensitizers that cross more efficiently the Pythium insidiosum membranes are able to cause extensive damage to the organism under illumination and therefore, are the best options for clinical treatment. [ABSTRACT FROM AUTHOR]