A Step forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach

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A Step forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach

Sexta, 15.01.2021



Eduardo Costa 1,2,3,4, Tânia Ferreira-Gonçalves 3, Miguel Cardoso 2,5,6,7, João M. P. Coelho 8, Maria Manuela Gaspar 3, Pedro Faísca 9, Lia Ascensão 10, António S. Cabrita 2, Catarina Pinto Reis 3,8,* and Isabel V. Figueiredo 1,7,*

1 Pharmacology and Pharmaceutical Care Laboratory, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;

2 Institute of Experimental Pathology, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;

3 iMed.ULisboa– Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal;

4 Vasco da Gama Research Group (CIVG), Vasco da Gama University School (EUVG), 3020-210 Coimbra, Portugal

5 Dentistry Area, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

6 Biophysics Institute, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

7 Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

8 Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal;

9 Faculty of Veterinary Medicine (ULHT)/IGC, 1749-024 Lisboa, Portugal;

10 Centro de Estudos do Ambiente e do Mar (CESAM), Universidade de Lisboa, Faculdade de Ciências, Campo Grande, 1749-016 Lisboa, Portugal;

* These authors contributed equally to this work.


Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors’ etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650-900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.

International Journal of Molecular Sciences

https://www.mdpi.com/1422-0067/21/24/9681