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)