Regioisomerism in NIR-II-emissive semiconducting biradicals for high-performance bioimaging and phototheranostics of tumors.

Abstract

Photothermal agents (PTAs) have received significant attention in medical therapeutic and diagnostic applications. Despite their tremendous development, developing PTAs is challenging when applied to a living body with deep tissue, as it usually leads to attenuated therapeutic efficiency and potential biosafety hazards. Here, we report a molecular isomerization strategy based on NIR-II semiconducting biradicals that boosts the performance of NIR-II phototheranostics. With a stereoisomeric design by precisely manipulating the substitution position of the alkyl side chain, the optimal isomer, α-TBTS, and its nanoparticles (NPs) provide enhanced NIR-II absorption and 63% photothermal conversion capabilities, resulting in efficient photoablation of tumor cells. Most importantly, the relationship between the molecular isomerism of these NIR-II theranostics enables enhanced NIR-II performance, which has been proven by theoretical and ultrafast spectroscopy studies. With all these advantages, the α-TBTS nanoplatform has simultaneously achieved high-resolution whole-body NIR-II angiography and trimodal tumor-targeted imaging in vivo. Moreover, α-TBTS NPs efficiently inhibited tumor growth without recurrence upon NIR-II light irradiation, providing good biosafety. This work demonstrates the feasibility of molecular isomerization in multimodal NIR-II biradical PTAs and thus provides a suitable theranostic agent for high-performance tumor phototheranostics.