CURCUMIN NANOVESICLES FOR INHALATORY PHOTODYNAMIC THERAPY

ALTUBE MARÍA JULIA; CAPUTO EZEQUIEL; MORILLA MARÍA JOSE; EDER LILIA ROMERO

Conferencia; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

SAIC-SAI-AAFE-NANOMEDAR

Curcumin (CUR) is a polyphenol obtained from the roots of Curcuma longa that produces singlet oxygen and other reactive oxygen species (ROS) when irradiated with blue light. In a previous workwe developed an inhalatory formulation of CUR encapsulated in archaeolipid nanovesicles, called nATC, and a conventional formulation of liposomal CUR, nLTC. While nATC had excellent stabilityagainst nebulization and long-term storage, nLTC released CUR after 1 month of storage and partially lost its CUR content during nebulization. Therefore, the aim of this work was to evaluate nATC as a photosensitizing agent to be used in an inhalatory photodynamic therapy (PDT) against lung cancer. We studied cytotoxic effects of nATC, nLTC and free CUR on A549 cells -a human lung adenocarcinoma cell line-, after irradiation at 420 nm with a fluence of 9 J/cm2. First, we determined cell proliferation by MTT 24 h after irradiation and obtained an IC50 of 3.7 ± 0.5 μM, 4.9 ± 0.8 μM and 8.5 ± 1.6 μM for nATC, nLTC and free CUR, respectively. Cells were labeledwith Annexin V/Propidium Iodide 6 h after irradiation and it was determined that only nATC induced apoptosis (12.5 ± 3% of cells analyzed by flow cytometry), while free CUR only induced necrosis (18± 2%). 24 h after irradiation, all formulations induced LDH release and complete depolarization of mitochondrial membrane potential. Furthermore, nATC and CUR completely inhibited cell migration 96 h post irradiation, whereas nLTC did not. Finally, only nATC was able to completely inhibit the activity of matrix metalloproteinases. These differential effects of nATC could be explained by 1) the higher cytoplasmatic CUR content within the cells and 2) the higher concentration of ROS and nitric oxide detected after nATC irradiation. We concluded that nATC outperformed liposomal CUR and free CUR making it a good candidate for inhalatory PDT that deserves further study to determine its anti-angiogenic activity and immunomodulatory effects.