Construction of smart switchable nanoplatforms for adaptive phototheranostics

Phototheranostics has emerged as an important branch of oncology, relying on multiple dissipation pathways of the excited state energy of phototheranostic agents to achieve disease diagnosis and therapy. However, the fixed excited-state energy dissipation pathways of conventional phototheranostic agents lead to inherent competition among diagnostic and therapeutic functions, ultimately compromising their efficacies in heterogeneous and dynamic tumor microenvironments (TMEs). The use of smart switchable phototheranostic platforms, which can dynamically redistribute photoenergy on demand to best fit the changed TMEs, has emerged as a transformative strategy to overcome this limitation. Their photo-functions could be smartly switched or adapted to maximize multimodal imaging and therapeutic performance. This review provides a comprehensive overview of the recent advancements in organic-based smart switchable phototheranostics, systematically categorizing them into five distinct design paradigms: (1) caging/uncaging molecular engineering, (2) dynamic assembly/disassembly, (3) manipulation of intramolecular motions, (4) photo-controlled molecular isomerization, and (5) metal-ion-involved redox-state transition. For each strategy, we elucidate the fundamental working principles and highlight representative examples that demonstrate tailored applications in adaptive phototheranostics. Finally, we discuss the prevailing challenges and future perspectives of these smart switching phototheranostic technologies. This review aims to inspire interdisciplinary research efforts for advancing precision oncology.