Book of abstract 2008

Photosensitizer-loaded nanoparticles for improving the efficacy and
selectivity of photodynamic therapy of tumours
C. Compagnin, L. Celotti, M. Mognato, E. Reddi
Dept. of Biology, University of Padova, Padova, Italy
Photodynamic therapy (PDT) is an innovative effective and minimally invasive therapy
against cancer and several non-oncological diseases. PDT is based on the concept that
some photosensitising molecules or photosensitisers (PSs) localise and are retained
preferentially in malignant tissues. Following activation with appropriate wavelengths of
red light, the PS generates reactive oxygen species (ROS) which cause oxidative damage to
various cellular components therefore leading to cell death. PDT induced cell death occur
through necrosis or apoptosis; the preferred mechanism is determined by the physicochemical
properties of the PS, the dose of PS and light, the characteristics of the tumour
cells. In addition to the direct damage to tumour cells, PDT causes alterations of the tumour
vascularization, with the consequent deprivation of oxygen and nutrients for cancer cells,
and stimulation of inflammatory and immune responses against the tumour. The relative
contribution of these pathways to the therapeutic effect depends on the distribution of PS
in the tumour compartments which is determined by its pharmacokinetic properties and
can be modulated by the PS administration and light illumination interval. The first PS
approved for clinical PDT is Photofrin®(hematoporphyrin derivative) whose performances
are far from optimal but is still the most largely used PS. More recently, Foscan® (tetrahydroxyphenyl
chlorin, mTHPC) has been introduced in the clinical practice for the
palliative treatment of head and neck advanced carcinomas. However for widening the
use of PDT to the treatment of various types of early stage localised tumours, it appears
of outmost importance to improve the efficacy and selectivity of PDT by increasing the
selectivity of the PS localisation. The entrapment of the PSs in nanosystems of different
nature is being investigated as a strategy to fully exploit the advantages that PDT offers
over conventional therapies. Therefore, liposomes and several biodegradable polymeric
nanoparticles
l40
have been used for the delivery of various types of PSs to tumour cells. In
addition, nanoparticles of non-biodegradable polymers have also been considered in spite
of some concerns about their safety. In all cases, most of the investigations with the PSloaded
nanoparticles have been carried with tumour cell lines in vitro while only a few in
vivo studies are reported.
The more recent and significant findings on the PS delivery with nanoparticles will
be discussed with the aim to critically evaluate the potential advantages offered by the
emerging nanomedicine for improving the efficacy and selectivity of PDT.
56