Nanoparticles for Photodynamic Therapy Applications - Intracellular Delivery: Fundamentals and Applications - page 514

accumulate selectively in tumor cells. Even if many efforts are focused on developing
third generation PS with a covalently linked vector to target receptors over-ex-
pressed in cancer cells, very few have been evaluated for clinical applications
mainly because their in vivo selectivity was not high enough (Taquet et al. 2007 ).
In order to address these issues, PS have been encapsulated in nanoparticles (NPs).
Indeed, encapsulation should lead to the administration of the PS in monomeric
form and without loss of the photophysical properties. More importantly, nanopar-
ticles can lead to selective accumulation of the PS in cancer tissue due to the
enhanced permeability and retention (EPR) effect of tumor tissues (Hoffman
2008 ). Therefore, nanoparticles have been suggested to improve the efficiency of
PDT. Liposomes, micelles, polymer-based nanoparticles and dendrimers which
can swell or change with the conditions (e.g. temperature, pH) will not be
described here: they have been reviewed recently (Allison et al. 2008 ; Bechet et al.
2008 ; Chatterjee et al. 2008 ). We will focus on nanoparticles possessing a three
dimensional rigid matrix such as metallic, metal-oxide, semi-conductor-based
nanoparticles or carbon nanotubes. Metallic nanoparticles (gold) have been used
as PDT drug carriers, and photothermal therapy, leading to a synergetic effect.
Metal oxide nanoparticles (Fe 3 O 4 ) are promising vectors for theranostics (Magnetic
Resonance Imaging, MRI, and PDT). ZnO and TiO 2 nanoparticles are able to gen-
erate ROS when irradiated with energetic UV-blue light. Alternatively, the use of
a photosensitizer with those nanoparticles allows irradiation with red light which
penetrates deeper inside tissues and creates less photo-damages. A variety of
precursors and methods are available for the syntheses of silica-based nanoparticles,
allowing flexibility and thus numerous PDT drugs to be encapsulated. Moreover,
particles size, shape, porosity and mono-dispersibility can be easily controlled during
their preparation (Wang et al. 2004 ). Semi-conductors-based nanoparticles
(quantum dots QD, silicon nanoparticles) can generate ROS by direct photo-
irradiation. The formation of ROS was also demonstrated by conjugation of QD
with photosensitizers through Förster Resonance Energy Transfer (FRET) mecha-
nism. Carbon nanotubes have been shown to be good delivery agents of PDT drugs
by electrostatic or covalent attachment of the photosensitizer with the nanotube.
All these nanosystems could be conjugated to a biomolecule or an antibody to
target receptors over-expressed in cancer cells, which enhance the selectivity of the
treatment. The very recent developments of nanosystems concern up-conversion or
two-photon PDT which opens new promising ways to treat deeper tissue regions
(Kim et al. 2007 ; Velusamy et al. 2009 ). Most of the studies with nanosystems
have been carried out in vitro , but in vivo PDT is currently being investigated
(He et al. 2009 ). Another field which grows rapidly consists in combining several
applications within one nano-object, such as MRI, fluorescence imaging and PDT
(Tada et al. 2007 ; Lai et al. 2008 ; Liu et al. 2008a ). Such multifunctional nanopar-
ticles emerge as important theranostic nano-objects. For clinical applications of
the present nanosystems further important studies are required: toxicology, bio-
compatibility, biodegradabililty, pharmacokinetics, biodistribution, clearance from
the body, dosimetry. These studies which are under way will open new perspec-
tives for the future of nanomedicine.