Integration of TADF Photosensitizer as “Electron Pump” and BSA as “Electron Reservoir” for Boosting Type I Photodynamic Therapy

Abstract

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by the tumor hypoxia. The challenge in the development of Type I mode is to boost the photosensitizer’s own electron transfer capacity. Herein, we found that the use of bovine serum albumin (BSA) to encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote the Type I PDT process to generate a mass of superoxide anions (O2 •–). This Type I photosensitization opened a new strategy by employing BSA as “electron reservoir” and TADF photosensitizer as “electron pump”. We integrated these roles of BSA and PS in one system by preparing nanophotosensitizer PS@BSA. The Type I PDT performance was demonstrated with tumor cells under hypoxic conditions. Furthermore, PS@BSA took full advantage of the tumor-targeting role of BSA and achieved efficient PDT for tumor-bearing mice in the in vivo experiments. This work provides an effective route to improve the PDT efficiency of hypoxic tumors.

Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia

“…There are some useful strategies for designing type I PSs: (1) promoting the ISC process to obtain enough triplets, which is necessary for both type I and type II PSs; (2) increasing the electron affinity of PSs, which facilitates electron capture to form stable free radical anion intermediates; (3) inhibiting the type II pathway by reducing the T1 energy level, which improves the competitiveness of type I pathway. For example, the presence of the azo group and CS bond was reported to boost ISC for an efficient PDT; 145 (4) utilizing of bovine serum albumin (BSA) to encapsulate a thermally activated delayed fluorescence photosensitizer; 146 (5) bypass oxygen to directly produce hydroxyl radicals through the oxidation of water in cells. 147 (6) Improving ROS generation efficiency through the polymerization effect that increasing the concentration of free radicals by increasing the stability of free radicals with aggregation.…”

Exploration of Thermally Activated Delayed Fluorescence (TADF)-Based Photoredox Catalyst To Establish the Mechanisms of Action for Photodynamic Therapy

“…In recent years, thermally activated delayed fluorescence (TADF) dyes have been developed and widely used in the preparation of OLED devices. − While the extremely small singlet–triplet energy gap (Δ E ST ) endows 100% internal quantum efficiency and long-lived luminescence through reverse intersystem crossing (RISC), it also enables them to be photosensitizers via intersystem crossing (ISC) . The TADF dyes have been used not only as time-gated imaging agents to reduce background interference and enhance fidelity, , but also as photosensitizers in PDT. − However, most TADF dyes are confronted with serious energy quenching in excited states due to aggregation . This great challenge would be circumvented with the intervention of aggregation-induced emission (AIE). , By integrating the structural commonalities of AIE and TADF in single molecule, several desired sensitizers have been developed successively. , In the aggregated state, the luminescent stability and sensitizing ability of these sensitizers enhanced markedly, the anti-interfering performance on O 2 also improved significantly, which was matched with the requirements of the aforementioned photoredox catalyst marvelously. ,, By scrutinizing the existing TADF-type photosensitizers, it was found that most of the sensitizers belong to PDT (II) − except a few PDT (I) , ones.…”

“…The TADF dyes have been used not only as time-gated imaging agents to reduce background interference and enhance fidelity, , but also as photosensitizers in PDT. − However, most TADF dyes are confronted with serious energy quenching in excited states due to aggregation . This great challenge would be circumvented with the intervention of aggregation-induced emission (AIE). , By integrating the structural commonalities of AIE and TADF in single molecule, several desired sensitizers have been developed successively. , In the aggregated state, the luminescent stability and sensitizing ability of these sensitizers enhanced markedly, the anti-interfering performance on O 2 also improved significantly, which was matched with the requirements of the aforementioned photoredox catalyst marvelously. ,, By scrutinizing the existing TADF-type photosensitizers, it was found that most of the sensitizers belong to PDT (II) − except a few PDT (I) , ones. There are scarce examples of TADF-type photosensitizers being applied in PDT based on MoA.…”

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

“…1,2 The functionality of PDT is, to a specific extent, dependent on the presence of oxygen. 3,4 The efficacy of PDT is significantly diminished in tumors, especially in large solid tumors, due to the presence of a hypoxic environment. 5,6 The integration of PDT with various other innovative therapeutic approaches, including photothermal therapy (PTT), photoacoustic therapy (PAT), photochemotherapy (PCT), and immunogenic cell death (ICD), has the potential to synergistically enhance treatment effectiveness and minimize the required dosage of therapeutic agents.…”

“…Photodynamic therapy (PDT) is a promising approach for cancer treatment, wherein the activation of photosensitizers (PSs) by light irradiation leads to the generation of reactive oxygen species (ROS). This process ultimately induces the noninvasive eradication of tumor cells. , The functionality of PDT is, to a specific extent, dependent on the presence of oxygen. , The efficacy of PDT is significantly diminished in tumors, especially in large solid tumors, due to the presence of a hypoxic environment. , The integration of PDT with various other innovative therapeutic approaches, including photothermal therapy (PTT), photoacoustic therapy (PAT), photochemotherapy (PCT), and immunogenic cell death (ICD), has the potential to synergistically enhance treatment effectiveness and minimize the required dosage of therapeutic agents. − Taking a step back to assert, for PDT alone, the mechanisms underlying the construction of highly active molecules or materials through structural regulation are considered to be largely unidentified. , …”