Photodynamic Therapy Using Novel Zinc Phthalocyanine Derivatives and a Diode  Laser for Superficial Tumors in  Experimental Animals

The purpose of this study was to evaluate the in vitro effect of the chlorophyllin–phycocyanin mixture (Photoactive+) as a photosensitizer (PS) during antimicrobial photodynamic therapy (aPDT) on the count of Enterococcus faecalis (E. faecalis) using different light sources. The antimicrobial effect of aPDT with chlorophyllin–phycocyanin mixture using different light sources including diode laser (λ = 660 nm), diode laser (λ = 635 nm), LED (λ = 450 ± 30 nm) alone or in combination was assessed using microbial cell viability assay against E. faecalis. In addition, the cell cytotoxicity of Photoactive+ was assessed on human gingival fibroblast (HuGu) cells by MTT assay; E. faecalis growth when treated by both red wavelengths (635 nm, 660 nm) and combination of LED (420–480 nm) and red wavelengths (635 nm, 660 nm), significantly reduced compared to the control group (p < 0.05). There was no significant reduction in the number of viable cells exposed to Photoactive+ compared to the control group (p < 0.05). This study shows that the application of chlorophyllin–phycocyanin mixture and irradiation with emission of red light achieved a better result for bacterial count reduction, compared to a control. This component can be applied safely due to very negligible cytotoxicity.

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Photosensitizers and Exposure Times To Light Showed Tissue Compatibility In Isogenic Mice

Brazilian Dental Science ◽

10.14295/bds.2021.v24i2.2340 ◽

2021 ◽

Vol 24 (2) ◽

Author(s):

Raquel Assed Bezerra da Silva ◽

Daniela Silva Barroso de Oliveira ◽

Katharina Morant Holanda de Oliveira ◽

Carolina Maschietto Pucinelli ◽

Paulo Nelson Filho ◽

...

Keyword(s):

Photodynamic Therapy ◽

Diode Laser ◽

Chloride Solution ◽

Light Exposure ◽

Subcutaneous Tissue ◽

Phase 1 ◽

Tissue Response ◽

Phase 2 ◽

Small Magnitude ◽

Tissue Compatibility

Objective: The aim of this study was to evaluate the subcutaneous tissue response after different protocols to photodynamic therapy (PDT). In Phase 1, were tested the diode laser (used for 1min) associated to the photosensitizer phenothiazine chloride solution (PCS) in different concentrations. In Phase 2 – the diode laser and LED were tested associated to two different photosensitizers, PCS and Curcumin, in different exposure times of light application. Material and Methods: After 7, 21 and 63-days the animals were euthanized and the subcutaneous tissue processed to histological analysis. Qualitative and semi-quantitative descriptions of the inflammatory process and immunohistochemical technique were performed. The obtained data were analyzed by Kruskal-Wallis and Dunn’s post-test (alpha = 0.5). Results: On Phase 1, the tissue response was very similar among the groups. For the inflammatory infiltrate, PCS with concentration of 10mg/mL exhibited the most intense reaction (p > 0.05). On Phase 2, at 7-days period, the analyzed parameters presented small magnitude and after 21 and 63-days, all the parameters demonstrated tissue compatibility. Conclusion: Both photosensitizers presented proper tissue compatibility regardless the different concentrations used on Phase 1 and different durations of light exposure on Phase 2. Keywords Photodynamic therapy; Phenothiazine chloride solution; Curcumin; Isogenic mice; Subcutaneous tissue.

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Zinc-Phthalocyanine-Loaded Extracellular Vesicles Increase Efficacy and Selectivity of Photodynamic Therapy in Co-Culture and Preclinical Models of Colon Cancer

Pharmaceutics ◽

10.3390/pharmaceutics13101547 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1547

Author(s):

Pablo Lara ◽

Ruben V. Huis in ‘t Veld ◽

Carla Jorquera-Cordero ◽

Alan B. Chan ◽

Ferry Ossendorp ◽

...

Keyword(s):

Colon Cancer ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Malignant Tumors ◽

Intratumoral Injection ◽

Zinc Phthalocyanine ◽

Tumor Cell Death ◽

Culture Models

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.

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