Capistrano Gustavo, Sousa-Junior Ailton A, Silva Roosevelt A, Mello-Andrade Francyelli, Cintra Emilio R, Santos Sônia, Nunes Allancer D, Lima Raisa M, Zufelato Nicholas, Oliveira André S, Pereira Maristela, Castro Carlos H, Lima Eliana M, Cardoso Clever G, Silveira-Lacerda Elisângela, Mendanha Sebastião A, Bakuzis Andris F
Instituto de Física, Universidade Federal de Goiás, 74690-900 Goiânia-GO, Brasil.
Nucleo Colaborativo de BioSistemas, Universidade Federal de Goiás, 75804-020 Jataí-GO, Brasil.
ACS Biomater Sci Eng. 2020 Aug 10;6(8):4523-4538. doi: 10.1021/acsbiomaterials.0c00164. Epub 2020 Jul 29.
IR-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. 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 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.
IR-780碘化物是一种在近红外区域具有光学特性的荧光染料，可应用于肿瘤检测及光热/光动力治疗。这种多功能效应促使了同时含有IR-780和多西他赛、阿霉素、氯尼达明等化疗药物的诊疗纳米颗粒的开发。在这项工作中，我们制备了两种含有近红外IR-780碘化物多功能染料的白蛋白基纳米颗粒，其中一种具有磁性核心。利用AutoDock Vina进行的分子对接研究表明，IR-780在较高温度下与牛血清白蛋白（BSA）结合更稳定，使得蛋白质结合口袋能更好地适配这种染料。理论分析证实了实验方案，即在60℃下，与30℃相比，即使在制备30天后，IR-780与BSA结合仍有增强。监测艾氏腹水癌细胞活力的实验揭示了无机磁性核心对纳米载体光热细胞毒性效应的重要性。对荷艾氏瘤的瑞士小鼠进行的荧光分子断层扫描测量显示了纳米载体的生物分布，在肿瘤组织中有明显蓄积（约3%注射剂量）。组织病理学分析表明，治疗后24小时和72小时肿瘤坏死区域显著增加，表明肿瘤消退。对未接受照射动物的肿瘤消退分析表明，IR-780具有剂量依赖性抗肿瘤作用，生存率高于70%（对动物监测长达600天）。此外，还进行了光热治疗程序，肿瘤消退也得到了证实。这些结果为基于IR-780-白蛋白的纳米载体在生物医学应用方面，即癌症治疗，提供了新的见解，不仅可通过光诱导治疗，还可通过非照射机制。安全性研究（急性口服毒性、心血管评估和组织病理学分析）表明其具有临床转化潜力。
