4 Photodynamic Therapy
Photodynamic therapy (PDT) uses light of the appropriate wavelength to activate a
chromophore, commonly known as photosensitizer (PS). The generation of the PS
singlet excited state is followed by intersystem crossing to the triplet excited state.
Thus, ground state molecular oxygen (triplet oxygen,
3 O 2 ) can quench the PS triplet
state by ET to generate singlet oxygen
1
Δ g , as well as by electron transfer to produce
reactive radicals; these reactive oxygen species (ROS) are capable of damaging
biomolecules and killing cells in the irradiated area [91, 92]. The extent of each
process will be determined by the photophysical features of the PS. For example,
ideally, for singlet oxygen generation, the PS would have very low fluorescence
quantum yield, high intersystem crossing quantum yield (Φ ISC ), long triplet lifetime
and high singlet oxygen sensitization (Φ Δ ).
Some of the limitations faced by common PSs are photobleaching, limited cellpenetrating capacity due to their easy aggregation and poor solubility in aqueous
solutions [93]. An approach that is being explored to circumvent these limitations is
the combination of photosensitizers and nanomaterials [94]. Hence, the search for
efficient PDT-photosensitizer/nanomaterial nanohybrids has been pursued in the last
decade. Silica nanoparticles [91], magnetic nanoparticles [94], quantum dots [95],
and metallic nanoparticles [96, 97] (among others) are examples of nanomaterials
used for this purpose.
Along this line, UCNPs are also being explored as functional carriers of PDT-PSs
in order to take advantage of their ability to absorb light in the NIR and use the
generated upconversion emission at the PSs absorption wavelength [39, 91]. For a
successful design, the PS selected to make an UCNH must absorb at the preferred
activator’s emission, to allow for NIR-induced LRET processes leading to pathway
(iv); that is, the PS absorbs the UCNP emission(s) leading to reactive oxygen
species [97].
The reader is referred to other revisions and book chapters for detailed methods of
synthetic protocols to make water-dispersible UCNPs [3, 5]. Briefly, coating UCNP S
with polymers or mesoporous silica to embed or attach PSs, grafting PSs onto the
UCNP surface and ligand exchange are the general methods for this purpose. Here
we focus on the right combination of UCNP composition and PSs according to their
photophysical features.
So far, for PDT applications, some PSs have been combined with UCNPs and are
presented in Chart 1: pyropheophorbide a [98], cationic porphyrin TMPyP4 [99],
riboflavin [100], I-BODIPY [2], rose bengal [101], methylene blue [33], zinc
phthalocyanine (ZnPc) [40, 102–105], fullerene derivatives (hyaluronated fullerene;
HAC 60 [106] and fullerene monomalonic acid; C 60 -MA [107]), Ru(bpy) 3
2+ [108],
hypericin [109], chlorin e6 (Ce6) [110, 111] and merocyanine 540 [112].
Zhang et al. [113] studied the distance-dependent RET between an UCNP,
β-NaYF 4 :20%Yb, 2%Er and an organic singlet oxygen generator, namely, rose
bengal. Er-doped UCNP was chosen because its maximum upconversion emission
band overlaps properly with the absorption band of the rose bengal. The donorFunctional Nanohybrids Based on Dyes and Upconversion Nanoparticles
387
Photodynamic therapy (PDT) uses light of the appropriate wavelength to activate a
chromophore, commonly known as photosensitizer (PS). The generation of the PS
singlet excited state is followed by intersystem crossing to the triplet excited state.
Thus, ground state molecular oxygen (triplet oxygen,
3 O 2 ) can quench the PS triplet
state by ET to generate singlet oxygen
1
Δ g , as well as by electron transfer to produce
reactive radicals; these reactive oxygen species (ROS) are capable of damaging
biomolecules and killing cells in the irradiated area [91, 92]. The extent of each
process will be determined by the photophysical features of the PS. For example,
ideally, for singlet oxygen generation, the PS would have very low fluorescence
quantum yield, high intersystem crossing quantum yield (Φ ISC ), long triplet lifetime
and high singlet oxygen sensitization (Φ Δ ).
Some of the limitations faced by common PSs are photobleaching, limited cellpenetrating capacity due to their easy aggregation and poor solubility in aqueous
solutions [93]. An approach that is being explored to circumvent these limitations is
the combination of photosensitizers and nanomaterials [94]. Hence, the search for
efficient PDT-photosensitizer/nanomaterial nanohybrids has been pursued in the last
decade. Silica nanoparticles [91], magnetic nanoparticles [94], quantum dots [95],
and metallic nanoparticles [96, 97] (among others) are examples of nanomaterials
used for this purpose.
Along this line, UCNPs are also being explored as functional carriers of PDT-PSs
in order to take advantage of their ability to absorb light in the NIR and use the
generated upconversion emission at the PSs absorption wavelength [39, 91]. For a
successful design, the PS selected to make an UCNH must absorb at the preferred
activator’s emission, to allow for NIR-induced LRET processes leading to pathway
(iv); that is, the PS absorbs the UCNP emission(s) leading to reactive oxygen
species [97].
The reader is referred to other revisions and book chapters for detailed methods of
synthetic protocols to make water-dispersible UCNPs [3, 5]. Briefly, coating UCNP S
with polymers or mesoporous silica to embed or attach PSs, grafting PSs onto the
UCNP surface and ligand exchange are the general methods for this purpose. Here
we focus on the right combination of UCNP composition and PSs according to their
photophysical features.
So far, for PDT applications, some PSs have been combined with UCNPs and are
presented in Chart 1: pyropheophorbide a [98], cationic porphyrin TMPyP4 [99],
riboflavin [100], I-BODIPY [2], rose bengal [101], methylene blue [33], zinc
phthalocyanine (ZnPc) [40, 102–105], fullerene derivatives (hyaluronated fullerene;
HAC 60 [106] and fullerene monomalonic acid; C 60 -MA [107]), Ru(bpy) 3
2+ [108],
hypericin [109], chlorin e6 (Ce6) [110, 111] and merocyanine 540 [112].
Zhang et al. [113] studied the distance-dependent RET between an UCNP,
β-NaYF 4 :20%Yb, 2%Er and an organic singlet oxygen generator, namely, rose
bengal. Er-doped UCNP was chosen because its maximum upconversion emission
band overlaps properly with the absorption band of the rose bengal. The donorFunctional Nanohybrids Based on Dyes and Upconversion Nanoparticles
387