4.5.2 Two-photon excitation donor type
Some two-photon absorbing fluorescent dyes can also be used to construct
energy transfer systems in photodynamic therapy. In the two-photon
excited FRET system, the combination of existing photosensitizers with
two-photon absorbing (TPA) dyes is utilized. Here, the photosensitizer
unit (energy acceptor) is indirectly excited by the fluorescence
resonance energy transfer of the two-photon absorbing dye unit (energy
donor). Energy capture by the TPA donor strongly enhances the two-photon
excitation efficiency of the photosensitizer, which in turn generates1O2 more efficiently(Bhawalkar et al.
1997; Dichtel et al. 2004). Since the two-photon absorbing donor can be
excited by near-infrared (NIR) light during this process, deeper tissue
penetration will be obtained compared to conventional PDT(Ogawa and
Kobuke 2008).
Kim and co-workers prepared organically modified silica nanoparticles
with 2-desethylene-2-(1-hexyloxyethyl) pyromellitic chlorophyll acid
(HPPH) as an energy acceptor and
9,10-bis(4′-(4′′-aminostyryl)styryl)anthracene dye with a severely
distorted geometry (BDSA) as a two-photon energy donor(Kim et al. 2007).
The two-photon absorption is enhanced by the partial flattening of the
aggregation geometry and the resulting loose stacking of molecules in
the aggregated state. At an excitation wavelength of 425 nm, the
fluorescence intensity of the co-wrapped nanoparticles is quenched by
about 70% for BDSA emission and amplified by about 5 times for HPPH
emission compared to the fluorescence intensity of nanoparticles
containing equal amounts of dye, respectively. It indicates that FRET
occurs between BDSA and HPPH, which enhances the production of1O2. Hammerer and co-workers attached
triethylene glycol (PTEGTP) or diethylene
glycol-α-mannosyl groups (PManTP) to meso-phenyl
moieties of porphyrins to obtain a series of porphyrin-triphenylamine
hybridized photosensitizers(Hammerer et al. 2018). These new
photosensitizers have a cationic charge in them and thus are extremely
water-soluble, thus improving cell penetration. Under 500 nm laser
irradiation, there is an energy transfer process from TP to porphyrin.
In addition, the new compounds were found to be localized in
mitochondria, the preferred target organelle for PDT. In conclusion, the
powerfully improved properties of the new photosensitizer significantly
increase the efficiency of two-photon activated PDT.
Semiconductor quantum dots are nanomaterials that hold great promise for
PDT applications. The size of quantum dots (QDs) gives them unique
optical properties that can be precisely tuned from the UV region to the
IR region by varying their size and composition. Due to the ability to
absorb in the near-infrared region of the spectrum, low intensity light
can be used to penetrate tissues, thus allowing access to deep tumors.
In addition, due to their large leap dipole moments, quantum dots are
excellent absorbing materials, making them ideal donors for activating
photosensitizers in PDT(Larson et al. 2003; Pu et al. 2006; Samia et al.
2003). (Fig. 10)