Photodynamic therapy is a treatment modality based on the combined action of three components: an agent that can be activated by light, known as a photosensitizer; light in the correct wavelength; and molecular oxygen. Individually, each of these three components does not induce toxicity, but when they act together, they unleash the production of reactive oxygen species that bring about cell death.

This study “analysed the potential of various compounds in the BODIPY family (4,4-difluoro-4 bora-3a,4a-diaza-s-indacene) as new photosensitizers, medicines used in photodynamic therapy. When cancer cells absorb it and are exposed to light, the drug is activated and the cancer cells are destroyed”, said Ruth Prieto-Montero, researcher in the UPV/EHU’s Molecular Spectroscopy Group.

“BODIPY dyes are highly fluorescent molecules. They also display great chemical versatility, which means that their structure can be very easily modified, thus facilitating the development of dyes with à la carte properties and with a whole host of applications,” explained the UPV/EHU researcher. That is why “in recent years they have been arousing great interest as fluorescent and/or photosensitizing probes and could be ideal candidates for the photodynamic diagnosis and treatment of a range of diseases, including cancer. But in general they have one big drawback: they are not soluble in aqueous mediums nor do they display a high degree of selectivity towards a specific biological target”, added Prieto. So right away, “this work focussed on firstly modifying the BODIPY molecule to improve its solubility in aqueous mediums and its selectivity towards specific organelles of the cell. To do this, hydrophilic groups and specific molecules, respectively, were added to the molecular structure of the dye, while its high fluorescent capability for use in bioimaging was maintained”, said the researcher in the UPV/EHU’s Molecular Spectroscopy Group. Secondly, these BODIPY dyes were modified for the purpose of developing enhanced photosensitizers with high phototoxicity and suitable for use in photodynamic therapy.

In addition, “three types of spherical silica nanoparticles approximately 50 nm in diameter were synthesised, and which together with a synthetic nanoclay (laponite) of about 100 nm, were used to carry commercial BODIPY-based dyes; silica is a compound that is biocompatible with the body and, what is more, does not absorb light, it is transparent. These nanosystems were also functionalized with polyethylene glycol and folic acid to improve their stability in water and selectivity towards tumour cells. That way, they accumulate mainly in cancer cells and not in healthy cells, and what we achieve is the selective death of the cancer cells when irradiated by the light”, said Prieto.

“The results achieved in the in vitro tests conducted with HeLa cells, a type of cell used in scientific research into cancer, are promising, because we saw that thanks to these systems 80% of the cancer cells die after 10-15 minutes of visible irradiation,” said Ruth Prieto.  Now “our idea would be to test it on various cell lines and cell tissue that contain both healthy and cancer cells to be able to actually confirm whether we are capable of selectively killing certain cells or others", concluded the researcher.

Additional information

This research was conducted within the framework of the PhD thesis by Ruth Prieto-Montero (Bilbao, 1992) entitled Novel systems for Bioimaging and Photodynamic Therapy: BODIPY dyes and silica-based nanocarriers. Her supervisors were Dr Virginia Martínez-Martinez, tenured researcher in the UPV/EHU’s Molecular Spectroscopy Group, and Iñigo López-Arbeloa, professor in the same group. The thesis was mostly written up in the Molecular Spectroscopy Group in the UPV/EHU’s Department of Physical Chemistry and had the collaboration of the following organisations: the Complutense University of Madrid, the Institute of General Organic Chemistry (IQOG), the Autonomous University of Madrid, the University of Oviedo, the Central Hospital of Asturias and the Technical Institute of Lisbon.