Produção Nacional
IR-780-Albumin-Based Nanocarriers Promote Tumor Regression Not Only from Phototherapy but Also by a Nonirradiation Mechanism
2020; American Chemical Society; Volume: 6; Issue: 8 Linguagem: Inglês
10.1021/acsbiomaterials.0c00164
ISSN2373-9878
AutoresGustavo Capistrano, Ailton A. Sousa-Junior, Roosevelt Alves da Silva, Francyelli Mello-Andrade, Emílio R. Cintra, Sônia F. O. Santos, Allancer Nunes, Raisa Melo Lima, Nícholas Zufelato, André Schneider de Oliveira, Maristela Pereira, Carlos H. Castro, Eliana Martins Lima, Cléver Gomes Cardoso, Elisângela de Paula Silveira-Lacerda, Sebastião Antônio Mendanha, Andris F. Bakuzis,
Tópico(s)Nanoparticle-Based Drug Delivery
ResumoIR-780 iodide is a fluorescent dye with optical properties in the near-infrared region that has applications in tumor detection and photothermal/photodynamic therapy. This multifunctional effect led to the development of theranostic nanoparticles with both IR-780 and chemotherapeutic drugs such as docetaxel, doxorubicin, and lonidamine. In this work, we developed two albumin-based nanoparticles containing near-infrared IR-780 iodide multifunctional dyes, one of them possessing a magnetic core. Molecular docking with AutoDock Vina studies showed that IR-780 binds to bovine serum albumin (BSA) with greater stability at a higher temperature, allowing the protein binding pocket to better fit this dye. The theoretical analysis corroborates the experimental protocols, where an enhancement of IR-780 was found coupled to BSA at 60 °C, even 30 days after preparation, in comparison to 30 °C. In vitro assays monitoring the viability of Ehrlich ascites carcinoma cells revealed the importance of the inorganic magnetic core on the nanocarrier photothermal–cytotoxic effect. Fluorescence molecular tomography measurements of Ehrlich tumor-bearing Swiss mice revealed the biodistribution of the nanocarriers, with marked accumulation in the tumor tissue (≈3% ID). The histopathological analysis demonstrated strong increase in tumoral necrosis areas after 24 and 72 h after treatment, indicating tumor regression. Tumor regression analysis of nonirradiated animals indicate a IR-780 dose-dependent antitumoral effect with survival rates higher than 70% (animals monitored up to 600 days). Furthermore, an in vivo photothermal therapy procedure was performed and tumor regression was also verified. These results show a novel insight for the biomedical application of IR-780-albumin-based nanocarriers, namely cancer therapy, not only by photoinduced therapy but also by a nonirradiation mechanism. Safety studies (acute oral toxicity, cardiovascular evaluation, and histopathological analysis) suggest potential for clinical translation.
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