Achieving beyond 100% Triplet State Generation with Singlet Fission Strategy for High-Performance Photosensitizer Design

Abstract

As the key of photodynamic therapy (PDT), the current photosensitizer (PS) design highly relies on promoting the intersystem crossing (ISC) process to form the triplet excited state, thus generating toxic reactive oxygen species (ROS). However, ISC is a spin-forbidden process with a low triplet state generation yield (<100%). Herein, as a proof of concept, we report a new strategy of aggregation induced singlet fission (SF) process with an ultrafast rate (<100 ps) and a very high triplet yield (>100%) to design efficient PSs. Such a unique SF strategy is demonstrated with an anthracene derivative of BPA-An, which shows Jaggregation enhanced ROS generation ability. Mechanism studies with aggregation behavior and fs-transient absorption spectroscopy indicate that BPA-An in Jaggregate state can efficiently generate triplet state via the SF process with a 158% triplet yield and thus possesses excellent Type-I and Type-II ROS generation ability in nanoparticle (NP) format. Both cellular and animal experiments further prove the excellent PDT antitumor performance of BPA-An NPs. To the best of our knowledge, this work shall represent the first example of utilizing SF as the design rule to promote the triplet state generation of PSs, which shall pave a new avenue in PDT.

TME-Triggered Degradable Phototheranostic Nanoplatform for NIR-II Fluorescence Bioimaging-Guided Phototherapies and Immune Activation

“…PDT, akin to PTT, employs photosensitizers to generate cytotoxic reactive oxygen species (ROS) upon light exposure, damaging tumor cells by disrupting cell membranes and intracellular biomacromolecules. − In addition, it has been reported that ROS can inhibit the activity of HSP, amplifying the effectiveness of PTT. − Compared to complex nanoplatforms loaded with both photothermal agents and photosensitizers, phototheranostic agents capable of generating both ROS and local heating offer simplicity and safety advantages in synergizing PTT and PDT. , Moreover, synergistic PTT and PDT induce stronger immunogenic cell death (ICD) response, which is characterized by the release of damage-associated molecular patterns (DAMPs) such as calreticulin (CRT) exposure, extracellular release of adenosine triphosphate (ATP), and high mobility group box B1 (HMGB1), and release tumor-associated antigens, activating the immune system and facilitating tumor eradication. − …”

Aromaticity Tuning of Heavy-Atom-Free Photosensitizers for Singlet Fission-Enhanced Immunogenic Photodynamic Oncotherapy

“…Recently, a DPND-based SF chromophore was developed with distinctive adaptive aromaticity and a high T 1 quantum yield of 173% . To date, SF molecules have demonstrated significant progress in photoenergy conversion. , However, rare SF molecules have been developed as photosensitizers with improved ROS for amplified PDT …”