Enhancing Type I Photochemistry in Photodynamic Therapy Under Near Infrared Light by Using Antennae–Fullerene Complexes

Abstract

Photodynamic therapy (PDT) has been developed as salvage or palliative treatment for a wide range of tumors. The principle underlying this therapy is the generation of reactive oxygen species through two types of photochemical pathways. As compared with the type II pathway, the type I pathway offers a higher oxidizing ability for photosensitive residues such as tryptophan, lower oxygen dependency, and deeper tissue penetration ability. In this review, we focus on the enhancement of the type I pathway in the near infrared (NIR) optical therapeutic window of wavelength 700-1,100 nm by using antennae-fullerene complexes. When photo-induced electron transfer occurs from antennas to fullerene, the pathway switches from type II to type I. Enhancing the type I pathway leads to less oxygen dependency and stronger capacity for tryptophan oxidation. Then, antennae that transfer long-wavelength light (e.g., NIR light) energy to fullerene via photo-induced energy and/or electron transfer have the ability to affect deep-seated tumors. On the basis of theories on photo-induced energy/electron transfer in other fields such as solar cells, here, we summarize the mechanism by which the switch from the type II to type I pathway occurs in antenna-fullerene-based PDT.

Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress

“…[19][20][21] Therefore, Type I PDT can achieve a better antihypoxia outcome. Up to now, several kinds of PSs following the Type I pathway have been reported to achieve signicant advances, such as antennae-fullerene conjugates, 12 inorganic nanocomposites, 22,23 organometallic complexes 24,25 and metalorganic frameworks. 26,27 However, for these complicated materials, the severe immunotoxicity, poor reproducibility and complex pharmacokinetics hinder their clinical application to some degree.…”

“…69,70 Actually, a wellestablished specic indicator for O 2 c À in cell-free systems is commercially scarce. 12 Accordingly, we decided to measure the secondary product, OHc, using hydroxyphenyl uorescein (HPF) to validate the Type I process. 65 Delightfully, a dramatically boosted uorescence signal is observed in the solution of HPF containing both nM BSA and 1 mM a-TPA-PIO or b-TPA-PIO aer 8 min of white light irradiation of 20 mW cm À2 , while only slight uorescence enhancement occurs for CV under the same conditions, indicating that a-TPA-PIO and b-TPA-PIO can distinctly and efficiently produce discernible OHc in the presence of a substrate ( Fig.…”

“…The more tumoricidal Type I PDT is regarded as a direct strategy with stronger hypoxia tolerance to overcome the limitations of traditional PDT that dominantly relies upon the Type II mechanism. 12,13 The so-called Type I and Type II mechanisms frequently discussed in PDT refer to two competing photoreaction pathways of ROS generation. [14][15][16] The former yields radical species (e.g.…”

Fighting Hypoxia to Improve PDT

“…One way is to provide additional O 2 in the areas to be treated by the addition of 1 O 2 itself, H 2 O 2 , or other molecules. Another way is to favour the formation of ROS at the expense of 1 O 2 by switching the photochemistry of PSs from a type II to a type I mechanism [15,16]. Some other interesting reviews on this topic can help in understanding the history, the notion of hypoxia and the broad scope of HBO [17][18][19].…”

Pyropheophorbide-Fullerene Dyad: Synthesis and Photochemical Properties

“…The creation of highly efficient photosensitizers that generate ROS by pathway I is of considerable interest since it is expected that they should be more effective in some cases, for example, against hypoxic tumors. [7] We have previously created dyads based on fullerene and dyes fluorescein, [8] ruboxyl [9] and chlorin, [10] which showed the high efficiency of ROS generation. For example, a tenfold increase in the superoxide generation efficiency by a fullerene-chlorin dyad in an aqueous solution (compared to a free chlorin) was shown.…”