Nanoparticles for Photodynamic Therapy Applications - Intracellular Delivery: Fundamentals and Applications - page 550

H 2 PtCl 6 /TiO 2 and H 2 PtCl6/SiO 2 were prepared by a sol-gel process using TEOS
and titanium butoxide as precursors. Hydrolysis was carried out at neutral pH and
H 2 PtCl 6 .6H 2 O was used as platinum precursor (Lopez et al. 1993, 1999 ). Titania was
further functionalized with a neurotransmitter in order to develop an analogy with
cells (Lopez-Goerne 2007 ). The obtained gels were dried to form solid nanoparti-
cles. The materials exhibit a high surface area together with a broad pore size dis-
tribution. The method of synthesis allowed obtaining high dispersed platinum metal
nanoparticles. In vitro DNA reactivity test of the biocatalysts were carried out by
electrophoresis and formation of DNA adducts was observed. The most active bio-
catalyst was H 2 PtCl 6 /SiO 2 . These biocatalysts were also tested in an experimental
model of C6 brain tumours in Wistar rats. Administration of the material was made
by stereotactic brain surgery to place it directly in the malignant tissue. A significant
decrease in tumour size and weight as well as morphologic changes in cancer cells
were observed. The platinum compound coordinates to DNA, probably by forming
bonds with DNA through hydrolysis of the phosphate group. The success of the
in vivo treatment is related to the modification of the surface properties of the titania
support enhancing the contact of the solid with the cell membrane, which permits to
deliver the Pt compounds at the damaged site. These particular features, besides the
high surface area of sol gel materials, lead to a major availability of platinum, mak-
ing possible to use lower platinum doses than systemic administration.
The same group investigated the possible synergy of zinc phthalocyanines
(ZnPc, Fig. 17 ) supported on TiO 2 nanoparticles and probed their in vitro photoac-
tivity using visible light, on cancer cells and Leishmania parasites (Lopez et al.
2010a ). They studied the photosensitizing effect of ZnPc, nano-TiO 2 , and ZnPc-
TiO 2 conjugate, against a panel of tumor and nontumor mammalian cells and on
promastigote forms of Leishmania parasites. As was expected, nano-TiO 2 alone
under visible light irradiation was not phototoxic for the cells; in contrast, ZnPc
treatment at the same condition was photoactive for all the studied cells and para-
sites. The composite ZnPc-TiO 2 was not phototoxic for L. Chagasi or L. Panamensis
promastigotes; however, it was active against tumor and nontumor mammalian cells
but less than the pure ZnPc PS. ZnPc-TiO 2 was internalized by the cells at a lower
level than ZnPc. The localization of ZnPc-TiO 2 and ZnPc were observed in mito-
chondrial cytoplasm. No fluorescence signal was observed in human-derived fibro-
blasts exposed to ZnPc-TiO 2 .

6.2 ZnO Nanoparticles

Thanks to its potential of non-toxicity, zinc oxide (ZnO) is a candidate for the
materials applicable for biomedicine (Dorfman et al. 2006b, 2006a ; Liu et al.
2008b ). Furthermore, among the PDT agents, ZnO is a material of particular inter-
est due to its unique optical and electronic properties, which has been widely used
for device applications including transducers, phosphors and varistors (Van De
Walle 2000 ). Currently, as a well known photosensitizer, ZnO nanoparticles could