ANTITUMORAL EFFICACY AND BIOSAFETY EVALUATION OF METALLATED PORPHYRIN-DOPED CONJUGATED POLYMER NANOPARTICLES FOR APPLICATION IN PHOTODYNAMIC THERAPY AGAINST GLIOBLASTOMA

CAVERZAN M.D.; PALACIOS R.E.; CHESTA C.A.; IBARRA L.E.

Rosario

Congreso; II REUNIÓN CIENTÍFICA INTERNACIONAL VII REUNIÓN CIENTÍFICA REGIONAL VI CONGRESO NACIONAL DE CIENCIA Y TECNOLOGÍA DE ANIMALES DE LABORATORIO; 2021

ACCYTAL

Malignant gliomas are more specifically glioblastomas (GBM)are considered as one of the most highly destructive brain diseases and the deadliest of human cancers. First-line treatment options such as surgery, radiation and chemotherapy have not been successful in increasing survival (12-15 months). Nowadays, the clinical application of photodynamic therapy (PDT) for malignant brain tumors has attracted significant attention. PDT combines light, a photosensitizer (PS) and molecular oxygen to generate reactive oxygen species (ROS) that cause damage to neoplastic cells. Some nanoparticles are excellent PSs due to their physicochemical characteristics. Recently, we have developed conjugated polymer nanoparticles (CPNs) using a fluorescent semiconductor polymer poly [(9,9-diocetylfluorenyl-2,7-diyl)-co-(1,4-benzo- {2,1′,3}-thiadiazole)] (F8BT); combined with PS-PEG polymer, and Pt (II) octaethylporphyrin (Ibarra, et al 2018, Caverzán, et al 2020). A preclinical evaluation related efficacy and safety in animals is mandatory for new potential CPN-based PSs. A human GBM cell line (U87MG) was used for the generation of heterotopic tumors in BALB/c nude (nu/nu) mice (Mus musculus). The PDT efficacy was evaluated using a dose of 0.4 mg/kg CPNs for intravenous (i.v.) and intratumoral (i.t.) injection followed by blue light irradiation (20 min, 13.3 mW/cm2). Furthermore, we evaluate serum biochemical parameters and histopathological changes in organs after CPN i.v. in healthy BALB/c mice at different times (24hs, 3, 7 and 14 days, n= 5) and compared with a control group (PBS i.v. injection). Alanine aminotransferase (ALT) and aspartate transaminase (AST) were considered biomarkers of liver damage. Besides, serum urea and creatinine values were determined to evaluate kidney damage. Histopathological analyzes were performed to examine structural features. Urea values were 58,4±4,6, 53,2±6.1, 75,4±14,8, 57±5,6 and 60±8,3 mg/dl for 24hs, 3d, 7d, 14d and control groups respectively. In addition, ALT values were 29±13,3; 33,2±12,7; 35,8±12,8; 25±4,8 and 28±2,9 for 24hs, 3d, 7d,14d and control groups respectively. The measurements of AST were 185,2±81; 297,6±146; 343±174; 148±26 and 174±31 for for 24hs, 3d, 7d, 14d and control groups respectively . Balb/c with heterotopic GBM presented serum urea values 53.8, ALT 45.6 and AST 314.8. It has been observed there are no significant variations in plasma urea and creatinine compared to the control group. Only on day 7 there was a slight increase in urea, but it?s normalizing on day 14.