Side chain engineering of semiconducting polymers for improved NIR-II fluorescence imaging and photothermal therapy

Abstract Development of efficient agents for NIR-II fluorescence imaging (NIR-II FI) offers opportunities to facilitate NIR-II FI in biomedicine and life science. Although semiconducting polymers (SPs) are proved to be excellent candidates for NIR-II FI, their fluorescence quantum yields are generally low mainly because of the accelerated nonradiative decay by the vibrational overlap between the ground state and excited state due to the small energy gap of NIR-II SPs. We herein propose a side chain engineering of SPs for enhanced NIR-II FI and imaging-guided photothermal therapy (PTT). The fluorescence optimization is realized by tuning the conformation and bulk of side chains of SPs, which demonstrates that the bulky branched side chains remarkably contribute to the fluorescence enhancement relative to linear or short branched side chains. Density functional theory (DFT) calculation indicates that bulky branched side chain-attached SP (P3) has the largest dihedral angle between electron donor and acceptor units, which suggests the largest intramolecular steric hindrance that restricts the free rotation in the molecule, thus boosting the radiative decay to generate fluorescence. Water-dispersible nanoparticles with high tumor specificity fabricated from the optimal P3 are employed for in vivo applications, which show excellent NIR-II FI performance and PTT efficacy toward tumor. Our study therefore proposes a feasible molecular guideline to amplify the NIR-II brightness of SPs for improved phototheranostics.