Two-photon photodynamic therapy

Ogawa K, Kobuke Y (2008) Recent advances in two-photon photodynamic therapy. Anticancer Agents Med Chem 8 269-279... 

Gao D, Agayan RR, Xu H, Philbert MA, Kopelman R (2006) Nanoparticles for two-photon photodynamic therapy in living cells. Nano Lett 6 2383-2386... 

Figure 17.8 Two-photon photodynamic therapy (PDT) (a) simultaneous absorption of two near-infrared (NIP) photons raises the sensitizer to the S, excited state (b) sequential absorption of two photons, one from S0 and the other from T, raises the sensitizer to a higher excited state...

This review describes some of the recent developments in materials which exhibit enhanced two-photon absorption that can initiate photopolymerization or up-converted emission. Various optical methods including femtosecond time-resolved pump-probe experiments to characterize the two-photon properties are discussed. Finally, the applications of two-photon processes to optical power limiting, up-converted lasing, 3-D data storage, 3-D micro-fabrication, two-photon fluorescence microscopy and bio-imaging, and two-photon photodynamic therapy are presented. 

Kim S, Ohulchanskyy TY, Pudavar HE, Pandey RK, Prasad PN (2007) Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dyes aggregates for two-photon photodynamic therapy. 

BhawaUcar JD, Kumar ND, Zhao CF, Prasad PN (1997) Two-photon photodynamic therapy. J Qin Laser Med Surg 15 201... 

Balaz M, Collins HA, Dahlstedt E, Anderson HL (2009) Synthesis of hydrophilic conjugated porphyrin dimers Pot one-photon and two-photon photodynamic therapy at NIR wavelengths. Org Biomol Chem 7 874—888... 

Ambjerg J, Jimenez-Banzo A, Paterson MJ et al (2007) Two-photon ab-sorption in tetra-phenylporphyeenes are porphycenes better eandidates than porphyrins for providing optimal optieal imrperties fm two-photon photodynamic therapy J Am Chem Soc 129 5188-5199... 

Silica nanoparhcles also have been developed for two-photon photodynamic therapy. Both, a novel two-photon fluorescent dye, 9,10-bis[4 -(4"-aminostyryl)styryl] anthracene (BDSA) and HPPH, have been incorporated into ORMOSIL nanoparticles made from VTES, using reverse microemulsion. The two-photon-induced intraparticle ERET, based on the use of two-photon fluorescent aggregates as donors and a photosensihzing drug as an acceptor, has been demonstrated [111]. 

Brevet, D., Basile, I., Maynadier, M., Vaillant, O., Mongin, O., Blanchard-Desce, M., Morere, A., Garcia, M., Durand, J.-O., and Raehm, L. (2011) Mannose-functionalized mesoporous silica nanoparticles for efficient two-photon photodynamic therapy of solid tumors. Angew. Chem., Int. Ed., 50 (48), 11425-11429. 

Ogawa K, Kobuke Y (2009) Design of two-photon absorbing materials for molecular optical memory and photodynamic therapy. Org Biomol Chem 7 2241-2246... 

All physical properties of pyrylium salts (unsubstituted or substituted with alkyl and/or aryl groups) prove the aromaticity of these cations vibrational spectra [66], mass-spectral fragmentations [67], magnetic properties [68-70], and electronic absorption spectra [71]. It should be mentioned that there is a close similarity between the electronic absorption bands of pyrylium salts and those of benzene, easily recognized by the marked bathochromic effect of substituents in y-position of pyrylium salts on one of these bands. Two-photon absorption spectra of 2,4,6-triarylpyrylium cations [72] may be used in optical data storage, lasing, and photodynamic therapy. 

Fig. 20. Process of the conventional photodynamic therapy (right) and the newly proposed approach based on two-photon process (left). PS photosensitizer TPC two-photon chromophore...

In this section we consider the role of molecular vibrations in resonant L NLO properties. Tliese properties govern the intensity of light absorption (or emission) accompanying tlie transition between two vibronic energy levels. Of interest here is one- and two-photon absorption (OPA and TPA). Applications of TPA, in particular, include three-dimensional optical data storage and photodynamic therapy. 

Since its theoretical prediction by GOppert-Mayer in 1931 [1], the nonlinear optical (NLO) process of two-photon absorption (TPA) has received considerable attention, owing to numerous relevant applications in several fields [2], such as optical limiting [3-5], three-dimensional microfabrication [7-15], up-converted lasering [16-18], photodynamic therapy [19-22], data storage [23-28], and biomedical imaging [29-33]. 

In addition, two-photon excitation can be another effective way to achieve NIR-triggered PDT/PTT synergistic therapy. For example, Li and coworkers also prepared hypocrellin-loaded AuNCs for two-photon PDT/PTT of cancer. The AuNCs were optimized to have efficient NIR absorption and further coated with lipids containing hydrophobic photosensitizer hypocrellin B (HB). The photodynamic effect of the photosensitizer was quenched in the Au nanostructure, thereby reducing side effects of the photosensitizer in unintended locations. For in vitro experiments, cancer cells were treated with the nanocomplex and irradiated with a 790 nm pulsed NIR laser. The photosensitizer HB was released from the AuNCs in the intracellular region, which induced dramatic phototoxicity due to the synergistic effect of PDT and PTT under two-photon irradiation. 

Notably a small number of cyclometalated platinum complexes have recently been developed for two-photon microscopy in cells. In 2008, Botchway et al. designed cyclometalated platinum complexes for two-photon excitation in cells with good photostability and low cytotoxicity. The complexes (for example compound 10) could rapidly enter cells and localised predominantly in the nucleus (see Fig. 10). Cyclometalated platinum complexes with potential for photodynamic therapy of tumours were developed by Selke et al. and imaged by fluorescence microscopy showing some uptake in the mitochondria and the nucleus. ... 

Furthermore, two-photon fluorescence microscopy was used to show that a cyclometalated platinum(II)-rhodamine complex 11 can act as a selective indicator for mercury(II) ions in aqueous solution, including when incubated in cells (Fig. 11). Luminescent cyclometalated platinum complexes were also designed for potential in photodynamic therapy, with a 2-(2 thienyl)polypyridyl complex synthesised by Selke et al. displaying potent photoactivity and localisation in mitochondria and the nucleus. ... 

Fisher WG, Partridge WP, Dees C, Wachter EA (1997) Simultaneous two-photon activation of type-I photodynamic therapy agents. Photochem Photobiol 66 141-155... 

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