IR-780-Albumin-Based Nanocarriers Promote Tumor Regression Not Only from Phototherapy but Also by a Nonirradiation Mechanism

体内分布 光热治疗 纳米载体 牛血清白蛋白 化学 医学 生物物理学 癌症研究 体内 阿霉素 纳米颗粒 体外 材料科学 纳米技术 生物化学 生物 化疗 内科学 生物技术
作者
Gustavo 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
出处
期刊:ACS Biomaterials Science & Engineering [American Chemical Society]
卷期号:6 (8): 4523-4538 被引量:22
标识
DOI:10.1021/acsbiomaterials.0c00164
摘要

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. 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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