INVESTIGADORES
CASAS Adriana Gabriela
congresos y reuniones científicas
Título:
?Aminolevulinic acid dendrimers in the treatment of cancer and atheromatous disease
Autor/es:
VAINMAN, M.; RODRIGUEZ L; DI VENOSA G; MAMONE L; GÁNDARA L; VALLECORSA P.; ROSSETTI MV; BATLLE A; BATTAH S; CASAS A
Lugar:
Lucerna
Reunión:
Congreso; International Congress of Porphyrins and Porphyrias; 2013
Resumen:
Photodynamic therapy (PDT) is an anticancer treatment
that involves administration of a tumour-localising photosensitizer and its
subsequent activation by visible light to result primarily in
singlet oxygen?induced photodamage to the tumour. The photosensitizer
absorbs light and in the presence of oxygen transfers energy, producing
short-lived cytotoxic oxygen species such as singlet oxygen or other oxygen
radicals.
The use
of endogenous protoporphyrin IX (PpIX) after administration of 5-aminolaevulinic
acid (ALA)
has led to many applications in PDT. However the efficacy of ALA-PDT is
sub-optimal for thicker tumours and improved ALA delivery and therapeutic response are
required. We have investigated the conjugation of ALA to a second-generation dendrimer for
enhancing porphyrin synthesis in vitro. Recent advances in
laser technology, and endovascular light delivery systems have broadened the
scope of PDT to include atherosclerotic applications, so called
Photoangioplasty.
The aim of this
work was to evaluate in vitro the
ability of ALA dendrimers 6m-ALA
and 9m-ALA to
photosensitize cancer cells and macrophages. We have focused on selectivity,
since the main aim is to damage macrophage component of the atheromatous plaque
while leaving intact the vasculature structures.
We have
employed the LM3 mammary carcinoma, the Raw 264.7 macrophage and HMEC-1
microvasculature cell lines. Porphyrins synthesised from the three cell lines were
evaluated fluorimetrically.
LM3,
HMEC-1 and Raw 264.7 cell lines
exposed to both 6m-ALA
and 9m-ALA reached complete ALA release from the nanocarriers 24 hr
after incubation.
On the
other hand, porphyrin synthesis is higher at 3 hr in macrophages (6m-ALA= 52 ± 6 µg porphyrins/105
cells, 9m-ALA= 59 ± 7 µg porph./105 cells) as compared to the
endothelial cell line (6m-ALA= 28 ± 3 µg porph./105 cells, 9m-ALA= 27 ± 2 µg porph/105
ccells) employing 0.2 mM
concentrations (p< 0,01), thus demonstrating selectivity of dendrimers for
macrophages.
In tumour
LM3 cells, PpIX from dendrimers is much higher as compared to ALA (ALA= 48 ± 6 µg porph./105
cells, 6m-ALA= 168 ± 19 µg porph/105 cells, 9m-ALA= 176 ± 20 µg porph/105
cells) at 3 hr employing 0.025
mM concentrations, showing the that dendrimers are much efficient than ALA for use in PDT of
cancer.