aluminum-phthalocyanine-disulfonate and Skin-Neoplasms

The objective of this study was to obtain optimized nanostructured lipid carriers (NLC) functionalized with chitosan containing chloroaluminum phthalocyanine (ClAlPc) as a photosensitizer. Initially, the optimization of the preparation method of the NLC was performed, where the influence of different surfactants such as PVA and Tween 80, as well as different solid lipids such as stearic acid and Glycerol Monostearate (GM) was evaluated. The formulation containing GM and PVA (NLC10) was considered promising. Following, by the adsorption method (NLC10q), the formulation was functionalized with chitosan and characterized. NLC10 and NLC10q presented sizes of 131.5 and 231.5 nm, and ZP of -24.30 and + 19.96 mV, respectively. The encapsulation efficiency of NLC10q was 96 %, higher than NLC10 (79 %). The formulations were able to promote significant cutaneous retention of ClAlPc, after 2 h and 4 h of the study, and showed to be non-toxic to fibroblasts (biocompatible). PDT in BF16-F10 melanoma resulted in reduced cell viability to 70 % and 50 % for NLC10 and NLCq, respectively. In view of the results obtained, NLC showed to be promising in the treatment of skin cancer through PDT. NLC10q showed higher encapsulation efficiency and stability than NLC10, but, contrary to what was expected, it presented lower photodynamic efficiency.

Topics: Chitosan; Drug Carriers; Glycerol; Humans; Indoles; Nanostructures; Organometallic Compounds; Particle Size; Photochemotherapy; Photosensitizing Agents; Polysorbates; Skin Neoplasms; Surface-Active Agents

Photodynamic therapy is a modality of treatment for tumors. The photochemical interactions of sensitizer, light and molecular oxygen produce reactive oxygen species (ROS) such as singlet oxygen, peroxide, hydroxyl radical and superoxide ion. The tumor is destroyed either by the formation of highly reactive singlet oxygen (type II mechanism) or by the formation of radical products (type 1 mechanism) generated in an energy transfer reaction. The resulting damage to organelles within malignant cells leads to tumor ablation. The cellular effects include membrane damage, mitochondrial damage and DNA damage. A new treatment modality called sonodynamic therapy has been developed, in which the ultrasound-induced cytotoxicity of sonochemical sensitizers inhibits tumor growth. In this study, the promising new generation of sensitizers - phthalocyanines - were used to induce the photodamage. In addition, we applied an ultrasound treatment to support the photodynamic effect. We report on the production of ROS in G361 melanoma cells. Light-emitting diodes were used to evoke the photodynamic effect. Changes in cells were evaluated using fluorescence microscope and atomic force microscopy. The quantitative ROS production changes in relation to sensitizer concentration, irradiation doses and ultrasound intensity were proved by a fluororeader. Our results showed the highest generation of ROS within G361 melanoma cells was achieved at an irradiation dose of 15 Jcm(-2) followed by ultrasound treatment at intensity of 2 Wcm(-2) and frequency of 1 MHz in the presence of 100 muM chloroaluminum phthalocyanine disulfonate (ClAlPcS2). These results suggest that ClAlPcS2 is a potential photosensitizer and sonosensitizer for sonodynamic or photodynamic treatment of cancer.

Topics: Cell Line, Tumor; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorometry; Humans; Indoles; Melanoma; Microscopy, Atomic Force; Microscopy, Fluorescence; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Skin Neoplasms; Treatment Outcome; Ultrasonic Therapy

In order to investigate the mechanism of action of photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPc) in squamous cell carcinoma, animal experiments were performed in induced carcinomas of the mucosa of the hamster's cheek pouch and skin of the laboratory mouse. Histological examinations revealed signs of massive interstitial bleeding, indicating a vascular response to PDT with AlSPc. It was also possible to induce similar change adjacent to newly formed vessels at the margin of an inflammatory reaction in the cheek pouch of five hamsters in the absence of tumor cells. Implanted human squamous cell carcinoma cells in athymic nude mice showed that carcinoma cells removed immediately following PDT remained viable, while tumors left in situ became necrotic. These results suggest that the primary effect of PDT with AlSPc in vivo is not the malignant cell itself, but the vascular stroma of the tumor or in the immediate vicinity of the latter.

Topics: Animals; Carcinoma, Squamous Cell; Cheek; Cricetinae; Indoles; Male; Mesocricetus; Mice; Mice, Nude; Mouth Mucosa; Mouth Neoplasms; Neoplasm Transplantation; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Skin Neoplasms