Photothermal agents based on small organic fluorophores with intramolecular motion

Photothermal therapy (PTT) has attracted great attention due to its noninvasive and low side effects. Photothermal agents (PTAs) which could convert absorbing light into heat play a critical role in PTT. For conventional small organic PTAs, the photothermal conversion ability is mainly achieved by intermolecular noncovalent interactions such as π-π interactions. However, in terms of organic fluorophores with rotator or vibrator segments, the balance between fluorescence emission and heat generation is mainly regulated by intramolecular motions which could be mediated by molecular engineering. Following this designing principle, various fluorophores with intramolecular motions for effective PTT have been reported. In this review, we highlight the recent progress of PTAs based on small organic fluorophores with intramolecular motions for enhanced PTT. Designing tactics of these fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation capability are emphasized. Finally, one-for-all phototheranostics achieved by mediating intramolecular motions of these fluorophores are highlighted. We hope this review could pave a new avenue to developing fluorophores with intramolecular motion as PTAs to advance their clinical transition. STATEMENT OF SIGNIFICANCE: Recent progress of photothermal agents (PTAs) based on small organic fluorophores with intramolecular motion is summarized in this review. Molecular engineering of these small organic fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation at tumor sites for enhanced photothermal therapy (PTT) is highlighted. Strategies to tune the intramolecular motions of these fluorophores to achieve multimodal phototherapy are emphasized as well.