| Autor: |
Hilda Angeline Quintos-Meneses, Liliana Aranda-Lara, Enrique Morales-Ávila, Blanca Ocampo-García, Irazú Contreras, Gerardo J. Ramírez-Nava, Clara L. Santos-Cuevas, José A. Estrada, Myrna A. Luna-Gutiérrez, Guillermina Ferro-Flores, Miguel A. Camacho-López, Eugenio Torres-García, Ninfa Ramírez-Durán, Keila Isaac-Olivé |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of Biomedical Nanotechnology. 17:2125-2141 |
| ISSN: |
1550-7033 |
| DOI: |
10.1166/jbn.2021.3179 |
| Popis: |
Recently, it was demonstrated that doxorubicin (Dox.HCl), a chemotherapeutic agent, could be photoactivated by Cerenkov radiation (CR). The objective of the present work was to develop a multimodal chemotherapy-radiotherapy-photodynamic therapeutic system based on reconstituted high-density lipoprotein (rHDL) loaded with Dox.HCl and 177Lu-DOTA. 177Lu acts as a therapeutic radionuclide and CR source. The system can be visualized by nuclear imaging. Fluorescence microscopy showed that rHDL-Dox specifically recognized cancer cells (T47D) that are positive for SR-B1 receptors. Encapsulated Dox.HCl was released into the cells and produced reactive oxygen species when irradiated with a 450-nm laser (photodynamic effect). The same effect occurred when Dox.HCl was irradiated by 177Lu CR. Through in vitro experiments, it was confirmed that the addition of 177Lu-DOTA to the rHDL-Dox nanosystem did not affect the specific recognition of SR-B1 receptors expressed in cells, or the cellular internalization of 177Lu-DOTA. The toxicity induced by the rHDL-Dox/177Lu nanosystem in cell lines with high (T47D and PC3), poor (H9C2) and almost-zero (human fibroblasts (FB)) expression of SR-B1 was evaluated in vitro and confirmed the synergy of the combined chemotherapy-radiotherapy-photodynamic therapeutic effect; this induced toxicity was proportional to the expression of the SR-B1 receptor on the surface of the cells used. The HDL-Dox/177Lu nanosystem experienced uptake by tumor cells and the liver-both tissues with high expression of SR-B1 receptors-but not by the heart. 177Lu CR offered the possibility of imparting photodynamic therapy where laser light could not reach. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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