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IR-780-Albumin-Based Nanocarriers Promote Tumor Regression Not Only from Phototherapy but Also by a Nonirradiation Mechanism
- Source :
- ACS biomaterials scienceengineering. 6(8)
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Biodistribution
Indoles
medicine.medical_treatment
0206 medical engineering
Biomedical Engineering
Photodynamic therapy
02 engineering and technology
Pharmacology
Ehrlich ascites carcinoma
Biomaterials
chemistry.chemical_compound
Mice
In vivo
Cell Line, Tumor
medicine
Animals
Tissue Distribution
Bovine serum albumin
biology
Lonidamine
Hyperthermia, Induced
Photothermal therapy
Phototherapy
021001 nanoscience & nanotechnology
020601 biomedical engineering
Molecular Docking Simulation
chemistry
biology.protein
Nanocarriers
0210 nano-technology
Subjects
Details
- ISSN :
- 23739878
- Volume :
- 6
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- ACS biomaterials scienceengineering
- Accession number :
- edsair.doi.dedup.....713d34809fe8e874e53d2b00b9ef4c97