Tumor Cell Death in Orthotopic Breast Cancer Model by NanoALA: A Novel Perspective on Photodynamic Therapy in Oncology

Abstract

Aim: Nano-5-aminolevulic acid (NanoALA)-mediated photodynamic therapy (PDT), an oil-in-water polymeric nanoemulsion of ALA, was evaluated in a murine model of breast cancer. Materials & methods: Analysis of ALA-derived protoporphyrin IX production and acute toxicity test, biocompatibility and treatment efficacy, and long-term effect of NanoALA-PDT on tumor progression were performed. Results: The nanoformulation favored the prodrug uptake by tumor cells in a shorter time (1.5 h). As a result, the adverse effects were negligible and the response rates for primary mammary tumor control were significantly improved. Tumor progression was slower after NanoALA-PDT treatment, providing longer survival. Conclusion: NanoALA is a good proactive drug candidate for PDT against cancer potentially applied as adjuvant/neoadjuvant intervention strategy for breast cancer.

Keywords::

• 4T1 cells
• 5-aminolevulinic acid
• breast cancer
• photodynamic therapy
• polymeric nanoemulsion

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2019-0458

Financial & competing interests disclosure

The authors gratefully acknowledge financial support from the Coordination for Further Training of Graduate Staff (CAPES), the Brazilian National Council for Technological and Scientific Development (CNPq), the Foundation to Support Research in the Federal District (FAPDF), Foundation for Research Support of the State of São Paulo (FAPESP, thematic project #2013/50181-1), Network of Nanobiotechnology CON-NANO (CAPES), National Institute of Science and Technology in Nanobiotechnology (INCT-Nanobiotecnologia), Center for Nanoscience and Nanobiotechnology of the University of Brasília (CNANO-UnB) and the Dean of Research and Post-Graduation of the University of Brasília (DPP-UnB). The authors have no other relevant affiliations or financial involvement with anyorganization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All experimental procedures were performed in accordance with the Animal Research Ethics Committee guidelines of the University of Brasilia, Brazil (CEUA number: 66707/2016). The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The authors gratefully acknowledge financial support from the Coordination for Further Training of Graduate Staff (CAPES), the Brazilian National Council for Technological and Scientific Development (CNPq), the Foundation to Support Research in the Federal District (FAPDF), Foundation for Research Support of the State of São Paulo (FAPESP, thematic project #2013/50181-1), Network of Nanobiotechnology CON-NANO (CAPES), National Institute of Science and Technology in Nanobiotechnology (INCT-Nanobiotecnologia), Center for Nanoscience and Nanobiotechnology of the University of Brasília (CNANO-UnB) and the Dean of Research and Post-Graduation of the University of Brasília (DPP-UnB). The authors have no other relevant affiliations or financial involvement with anyorganization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.