Molecular Design for Stable Near-Infrared-II Two-Photon Excitation-Induced Photoacoustic Contrast Agents Based on Donor-Substituted BODIPYs

We present the synthesis of donor-acceptor-type bis(triisopropylsilyl-ethynyl)-substituted boron-dipyrromethene (BODIPY) derivatives (2 and 5) with the capability for concerted two-photon (TP) excitation-induced photoacoustic (PA) imaging by near-infrared-II (NIR-II) light irradiation. The absorption spectra of these BODIPYs exhibited distinct and intense peaks within the NIR-I region. Along with this feature, the emission properties of compounds 2 and 5 are notably weak due to their intramolecular charge transfer character. Incorporating bulky peripheral substituents in 2 and 5 facilitated the encapsulation of these dyes into bipolar, water-soluble nanoparticles. The resulting micelle solution of 2 exhibited TP-PA signals produced by a nanosecond pulsed laser, displaying a stronger signal intensity than 5. This study indicated the importance of the electronic coupling between the donor substituents and BODIPY core, which would contribute to developing design guidelines for TP-PA agents used in deep in vivo imaging applications.