The Orthogonal α-meso-Linked bisBODIPY Photosensitizers Demonstrate Effective Two-Photon Fluorescence Imaging and Photodynamic Therapy

Abstract

Hypoxic tumor microenvironments pose significant challenges to the clinical translation of cancer photodynamic therapy (PDT). While heavy atom-free Type-I boron dipyrromethenes (BODIPYs) photosensitizers can alleviate this challenge by reducing oxygen dependency, but they remain scarce. Herein, heavy-atom-free α,meso-linked bisBODIPYs were designed and synthesized. These bisBODIPYs exhibit remarkable red-shifted emission (λemmax ~670 nm), large Stokes shifts (~4480 cm⁻¹) and they are capable of producing both superoxide anion (O₂⋅⁻) and singlet oxygen (¹O₂) in solution and cells. Additionally, they offer a wide PDT treatment window, ranging from 0.26 to 83.5 μM. Furthermore, these bisBODIPYs also demonstrate superior two-photon fluorescence, promising for surgical navigation and integrating diagnosis with treatment.