Design of Photostable, Activatable Near‐Infrared Photoacoustic Probes Using Tautomeric Benziphthalocyanine as a Platform

Abstract

Near‐infrared (NIR) imaging techniques have attracted significant attention for biological and medicinal applications due to the ability of NIR to penetrate deeply into tissues. However, there are very few stable, activatable molecular probes that can utilize NIR light in the wavelength range beyond 800 nm. Herein, we report a new activatable NIR system for photoacoustic imaging based on tautomeric benziphthalocyanines (BPcs). We found that the existence of a free hydroxyl group is crucial for NIR absorption of BPcs. Synthesized water‐soluble hydroxy BPcs exhibited high photostability and no fluorescence, which are desirable features for photoacoustic imaging. We synthesized BPcs in which the free hydroxyl group was masked by an esterase‐labile or an H2O2‐labile group. The photoacoustic signals of these hydroxy‐masked BPcs were increased upon NIR excitation at 880 nm in the presence of esterase or H2O2, respectively. These are rare examples of activatable probes utilizing NIR light at around 900 nm.

New contrast agents for photoacoustic imaging and theranostics: Recent 5-year overview on phthalocyanine/naphthalocyanine-based nanoparticles

“…Toriumi et al reported tautomeric benziphthalocyanines, by introducing free hydroxyl group with esterase- or H 2 O 2 -labile markers, for activatable PA detection of esterase or H 2 O 2 . 55 Xie et al designed Pc-based semiconducting macromolecule, which first underwent ROS-induced cleavage process of PEG and then subsequently the residual Pcs self-assembled into large nanoparticles, showing enhanced PA signal [ Fig. 5(b) ] in the presence of ROS.…”

Photoacoustic Imaging Probes Based on Tetrapyrroles and Related Compounds

“…Uchiyama and coworkers approached the ROS detection with a novel design inspired by Pc, namely benziphthalocyanine (BPc, 14c), incorporating a phenol in the Pc macrocycle (Figure 11) [102]. The BPc exhibited a quinoid-phenolic equilibrium and a high photostability, as Pcs, but weak NIR absorption 870 nm (ε = 1.64 × 10 3 M −1 cm −1 ) and no fluorescence emission.…”

Design Strategies of Photoacoustic Molecular Probes

“…Naoyuki et al. reported a novel activatable system of the PA probe which was constructed based on benziphthalocyanines (BPcs) [43] . They found BPc with a free hydroxy group existed as a tautomeric mixture of a weakly phenol form ( 8 c , 6π‐conjugation) and a strongly quinoidal form (18π‐conjugation) in solution.…”