Deciphering the intersystem crossing in near-infrared BODIPY photosensitizers for highly efficient photodynamic therapy

Abstract

Deciphering singlet-to-triplet intersystem crossing (ISC) in organic near-infrared photosensitizers (PSs) is of fundamental importance in the designing of high-performance PSs to boost the clinical usage of photodynamic therapy (PDT). However, in-depth investigations of the ISC dynamics in near-infrared PSs have not been performed to date. Here, systematical investigations of the ISC dynamics in organic near-infrared BODIPY derivatives are presented, in which a multi-channel yet remarkably efficient ISC process is revealed by ultrafast femtosecond transient absorption (fs-TA) spectroscopy and theoretical calculation. The fs-TA verifies an exceptionally enhanced ISC efficiency (Φ _ISC = 91%) in iodine-substituted BODIPY (2I-BDP) which is further supported by the calculation results. This endows 2I-BDP with an ultrahigh singlet oxygen quantum yield (Φ _Δ = 88%), thus enabling a proof-of-concept application of highly efficient PDT in vivo under ultralow near-infrared light power density (10 mW cm^-2). The in-depth understanding of ISC dynamics in organic near-infrared materials may provide valuable guidance in the designing of novel organic theranostic materials for clinical cancer treatment.

Scheme 1. Molecular structures and photophysical properties of BDP and 2I-BDP.

Fig. 1. (a) Normalized absorption spectra of BDP and 2I-BDP in methanol. (b) Photoluminescence (PL) spectra of BDP and 2I-BDP in methanol. Inset is their digital photos irradiated by corresponding absorption maxima. (c) Time-resolved photoluminescence decay transients of BDP and 2I-BDP in the specific emission ranges. The optical excitation is performed with 650 nm pump pulses (50 fs, 50 MHz). (d) Characteristic ¹O₂ emission of BDP and 2I-BDP in the deuterated method.

Fig. 2. (a, b) 2D pseudocolor fs-TA spectra of BDP and 2I-BDP in methanol (0.1 mg mL^–1) following photoexcitation with a 650 nm laser pulse. The ground state absorption spectrum is presented in the top panel as dashed lines. (c, d) fs-TA spectra of BDP and 2I-BDP at different pump-probe delay times. (e, f) Kinetic traces and fitting lines of BDP and 2I-BDP taken through the representative singlet and triplet ESA peaks. (g) Schematic diagrams showing the computed energy levels and the probably occurring channels of ISC from the S₁ state to its higher- or lower-lying triplet states (T_n) possible. The triplet states marked in red contain the same transition components as S₁. Average spin–orbit coupling (SOC) matrix elements between the respective singlet and triplet states (the larger the SOC value, the higher the possibility of ISC). (h) Schematic representation of ISC dynamics and photosensitization processes taking place in 2I-BDP. Fl: fluorescence, Phos: phosphorescence, and IC: internal conversion.

Fig. 3. (a) Confocal fluorescence images of MCF-7 cells incubated with DCF-FA and 2I-BDP under LED lamp irradiation. The scale bars are 100 μm. (b) Live/dead assay of MCF-7 cells. Green colour represents live cells, and red colour represents dead cells. The scale bars are 140 μm. (c) The tumor growth curves with different treatments. Error bars indicate SD (n = 6). (d) Gross solid tumor images of mice injected with different formulations 17 days post treatment. (e) The representative of the tumor sections examined by H&E staining and TUNEL. The scale bars are 100 μm.