A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light

Abstract

The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.

Application of nanotechnology for enhancing photodynamic therapy via ameliorating, neglecting, or exploiting tumor hypoxia

“…Although the fractional PDT allows time for the replenishment of cellular oxygen, some other issues such as irradiation dependence, rapid metabolism of organic photosensitizers, and extended therapeutic cycles still need to be overcome. Hence, to further enhance the availability of fractional PDT, Akkaya et al designed a bifunctional boron‐dipyrromethene (BODIPY)‐based fractional PDT system, in which a 2‐pyridone group was grafted into the structure of BODIPY 88 . The reversible transformation between the 2‐pyridone (PYR) moiety and its endoperoxide (EPO) derivative enables continuous 1 O 2 generation under both the light and dark phases of the cycle (Figure 6A).…”

“…(A) The basic principle of a fractional PDT using 2‐pyridone conjugated BODIPY. Reprinted with permission 88 . Copyright 2016, Wiley‐VCH.…”

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…As a burgeoning cancer tool, phototherapy offers specific spatiotemporal selectivity and minimal invasion into healthy tissues . Phototherapy generally involves the activation of photosensitizers (PSs) under light irradiation to induce cancer cell phototoxicity by generating reactive oxygen species (ROS) (photodynamic therapy, PDT) or heating via nonradiative relaxation pathways (photothermal therapy, PTT) …”

“…Boron dipyrromethene (BODIPY) has attracted much interest with respect to cancer phototherapy because it possesses unique chemical and physical properties: intense absorption at relatively long wavelength, long triplet excited state lifetime, and excellent photostability . In addition, BODIPY synthesis and modification are facile and readily controllable . Moreover, BODIPY‐containing nanoparticles as nano‐photosensitizers were constructed by polymer encapsulation, dye precipitation, or host–guest interactions.…”

pH‐Triggered 4,4′,4′′,4′′′‐(Ethene‐1,1,2,2‐tetrayl)tetrakis(N,N‐diethylaniline) with Aggregation‐Induced Emission (AIE) for Ablation of Cancer Cells

“…Photodynamic therapy (PDT), as a newly developed one, has attracted increase attention owing to its non‐invasion, low cytotoxicity, good biocompatibility, etc . The key to PDT is the design and preparation of photosensitizers (PS), which can generate reactive oxygen species (ROS) under the irradiation of light.…”