Access to the Triplet Excited States of Heavy-Atom-Free Boron-Dipyrromethene Photosensitizers via Radical Pair Intersystem Crossing for Image-Guided Tumor-Targeted Photodynamic Therapy

Abstract

Boron-dipyrromethene (BODIPY) dyes have aroused considerable interest in cancer theranostics over the past decade because of robust photochemical properties. Although a large number of BODIPY photosensitizers (PSs) containing heavy atoms have been reported, the development of heavy-atom-free BODIPY PSs for oncologic photodynamic therapy (PDT) has been limited mainly by the uncertainty in intersystem crossing (ISC) mechanisms, unbalanced phototoxic effectiveness and fluorescence quantum yields, and aggregation-caused quenching effects. In addition, the lack of extensive in vivo studies of heavy-atom-free BODIPY PSs continues to limit clinical application. Herein, novel heavy-atom-free BODIPY-phenoxazine triads (BDP-8/BDP-9) that generate efficient excited triplet states via radical pair intersystem crossing (RP-ISC) followed by triplet charge recombination were developed for use in fluorescence image-guided PDT. BDP-8/BDP-9 exhibited high molar absorption coefficients, prominent aggregation-induced emission, and excellent singlet oxygen generation capability upon light irradiation. The corresponding BODIPY nanoparticles (BDP-8/BDP-9 NPs) with bright red emission, considerable phototoxicity, and excellent tumor-targeting ability were simply prepared by encapsulating BDP-8/BDP-9 PSs in a polymeric matrix. More importantly, the results of both in vitro and in vivo experiments demonstrated the considerable potential of BDP-8 NPs for image-guided photodynamic cancer therapy. This study may inspire the development of potential BODIPY-based nanoagents for cancer theranostics.

Rational Molecular Design of Efficient Heavy‐Atom‐Free Photosensitizers for Cancer Photodynamic Therapy

“…Next, the phototherapeutic effect of PTZ‐CN/PXZ‐CN was quantitatively evaluated on HeLa cells using the standard 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay [14] . Upon blue light irradiation, the cell viability gradually decreased with increasing concentration of PTZ‐CN/PXZ‐CN (Figures 5a and 5b).…”

“…Intracellular ROS generation was also determined, and a bright green fluorescence signal was detected (Figures 5c, d Next, the phototherapeutic effect of PTZ-CN/PXZ-CN was quantitatively evaluated on HeLa cells using the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. [14] Upon blue light irradiation, the cell viability gradually decreased with increasing concentration of PTZ-CN/ PXZ-CN (Figures 5a and 5b). The phototherapeutic efficacy of PTZ-CN was superior to that of PXZ-CN, with a half-maximal inhibitory concentration (IC 50 ) of ca.…”

Organic conjugated small molecules with donor–acceptor structures: design and application in the phototherapy of tumors

“…Enhanced ICT could reduce the bandgaps to improve the ISC rate of the photosensitizers, 84 which is beneficial for enhancing the PDT activity. 85,86 So the core of the current molecular design is how to improve the interactions between the D and A units. One strategy is to use conjugated units with a higher electron-donating or electron-withdrawing capability.…”

Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application

“…A complete understanding of ISC mechanism contributes to the design and application of functional BODIPY-type PSs. Nguyen et al 89 developed two new heavy-atom-free AIE PSs (BDP-8/BDP-9) based on the BODIPY structure with tumor-targeting ability for image-guided PDT (Fig. 11).…”