RESUMO
INTRODUCTION: Nanoparticles (Np) can increase drug efficacy and overcome problems associated with solubility and aggregation in a solution of PpIX. PURPOSE: Evaluate if Np interferes in the photophysical and photobiological capacity of the PpIX comparing with free PpIX intended for topical PDT of melanoma. METHODS: In vitro photophysical evaluation of Np-PpIX was carried out through singlet oxygen (1O2) quantum yield. In vitro cytotoxicity and phototoxicity assays have used murine melanoma cell culture. RESULTS: The quantum yield of singlet oxygen has shown that Np did not influence the formation capacity of this reactive species. In the dark, all PpIX-Nps concentrations were less cytotoxic compared to free drugs. At a higher light dose (1500â¯mJ.cm2) 3.91⯵g / mL PpIX had similar % viable cells for free and Np (â¼34 %) meaning Nps did not interfere in the photodynamic effect of PpIX. However, at 7.91⯵g / mL the phototoxicity increased for both (5.8 % viable cells for free versus 21.7 % for Nps). Despite the higher phototoxicity of free PpIX at this concentration, greater cytotoxicity in the dark was obtained (â¼49 % viable cells for free versus â¼90.6 % Np) which means Nps protect the tumor tissue from the photodynamic action of PpIX. CONCLUSIONS: Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability â¼80 % (7.91⯵g / mL PpIX in Nps) and provides safe PDT (due to lower cytotoxicity in the dark).
Assuntos
Melanoma , Nanopartículas , Fotoquimioterapia , Animais , Melanoma/tratamento farmacológico , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , ProtoporfirinasRESUMO
Photosensitizers (PS) are compounds that can generate reactive oxygen species under irradiation of appropriate light and are widely used in photodynamic therapy (PDT). Currently, topical PDT is an effective treatment for several skin diseases, including bacterial infections, fungal mycoses and psoriasis. In addition, PDT is also used to treat nonmelanoma skin cancer and can be a potential tool for melanoma, associated with other treatments. In this work, we evaluated the antitumor photoactivity of a new pyrene-based PS (TPPy) by using the murine melanoma cell line (B16F10). The in vitro permeation/retention tests in porcine ear skin were also performed in order to evaluate the potential application of the PS for topical use in skin cancer. Moreover, to determine the toxicity in vivo, we used the Galleria mellonella as an alternative animal model of study. The results showed that TPPy is a promising PS for application in PDT, with potential antitumor photoactivity (IC50 6.5 µmol L-1 ), absence of toxicity in the G. mellonella model at higher concentration (70.0 mmol L-1 ) and the accumulation tendency in the epidermis plus dermis sites (165.20 ± 4.12 ng cm-2 ).
Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/química , Fotoquimioterapia/métodos , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Pele/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , SuínosRESUMO
In the present study, SiO2 nanoparticles functionalized with 3-(2-aminoethylamino)propyl group (SiNP-AAP) were used, for the first time, to covalently bond rose bengal (SiNP-AAP-RB) or 9,10-anthraquinone-2-carboxylic acid (SiNP-AAP-OCAq). The functionalized SiNP were characterized by: Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM); elemental analysis (CHN) for determination of the dye concentration; FTIR and UV-vis diffuse reflectance (DR-UV-vis) and a surface area study (BET). The functionalized SiNPs were applied in photodynamic therapy (PDT) against lung cancer cell lines. The evaluated cytotoxicity revealed 20-30% cell survival after 15min of PDT for both materials but the OCAq concentration was half of the RB nanomaterial. The phototoxicity was mainly related to oxidative stress generated in the cellular environment by singlet oxygen and by hydrogen abstraction as confirmed by the laser flash photolysis technique. The unprecedented results indicate that SiNP-AAP-OCAq is a possible system for promoting cell apoptosis by both type I and type II mechanisms.