Photosensitizers for Two‐Photon Excited Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a noninvasive protocol for the treatment of various cancers and nonmalignant diseases. Light, oxygen, and photosensitizer (PS) are the essential three elements in a typical PDT process. Currently, there are two major barriers limiting the further development of PDT. One issue is limited tissue penetration, and the other is the lack of high-performance PSs. Therefore, the newly emerging two-photon excited PDT (2PE-PDT) has attracted considerable attention in recent years due to its advantages such as a higher spatial resolution and a greater penetration depth. In this review, focus is on (i) the principle of 2PE-PDT, (ii) the progression of PSs for 2PE-PDT, and (iii) the potential indications and future directions in this field.

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

“…In addition, 2-photon PDT also improves the spatial selectivity and reduces photodamage to healthy tissues (15,16). The efficiency of 2-photon light absorption, also known as the 2-photon absorption cross-section, is crucial for the therapeutic efficiency of the PSs (15,(17)(18)(19). However, the utility of existing clinical PSs for in vivo 2-photon PDT is hampered due to their low 2photon absorption cross-sections: on the order of 1 to 100 Goeppert Mayer (GM) units (1 GM = 10 −50 cm 4 s photon −1 ) ( [20][21][22].…”

Phthalocyanine-Cored Fluorophores with Fluorene-Containing Peripheral Two-Photon Antennae as Photosensitizers for Singlet Oxygen Generation

“…Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.Molecules 2020, 25, 239 2 of 30 studying new porphyrin-or phthalocyanine-based molecular assemblies that might efficiently undergo two-photon excitation [10-13] while presenting a significant luminescence, constitutes an appealing goal for researchers interested in developing new photosensitizers for theranostic applications [4,5,[14][15][16]. Along these lines, some of us [17,18] and others [19], independently reported that fluorenyl units, when appended at the meso positions of porphyrins, were particularly suited to enhance the fluorescence quantum yields of this macrocyclic core, most likely by limiting the rate of non-radiative decay via internal conversion [20].…”

“…As a result, new oxygen photosensitizers with significantly improved brightness over H 2 TPP could be obtained by these means [25]. Furthermore, the presence of several fluorenyl units at the periphery of the central macrocycle also allowed for a significant increase in the two-photon absorption (2PA) cross-section maximum at lowest energy, another very desirable feature when targeting PDT or theranostic applications in the near-infrared (NIR) range [14,15].We can notice that, after having studied these non-conjugated TPP-based porphyrin dendrimers featuring flexible ether linkers (Figure 1), we considered more recently porphyrin dendrimers with conjugated peripheral arms [26]. Thus, a series of meso-substituted porphyrin dendrimers incorporating an increasing number of fluorenyl units, featuring fully conjugated alkynyl linkers, was studied.…”

“…As a result, new oxygen photosensitizers with significantly improved brightness over H 2 TPP could be obtained by these means [25]. Furthermore, the presence of several fluorenyl units at the periphery of the central macrocycle also allowed for a significant increase in the two-photon absorption (2PA) cross-section maximum at lowest energy, another very desirable feature when targeting PDT or theranostic applications in the near-infrared (NIR) range [14,15].…”

Screening of two-photon activated photodynamic therapy sensitizers using a 3D osteosarcoma model

“…Relaxation occurs via the Type I or Type II reaction with molecular oxygen as described previously. 11 Due to the nonlinear behaviour of the absorption process, high peak power lasers such as modelocked Ti:sapphire lasers with femtosecond pulse durations are required to achieve efficient two-photon absorption. 12 Different photosensitizers have been developed for TPE-PDT applications, including porphyrin derivatives, ruthenium complexes, conjugated polymers, and nanoparticles.…”