A simple strategy for simultaneously enhancing photostability and mitochondrial-targeting stability of near-infrared fluorophores for multimodal imaging-guided photothermal therapy.

Near-infrared fluorophores are emerging as promising molecular tools for cancer theranostics because of their inherent biodegradability, low toxicity, and synthetic flexibility. However, they still suffer from several limitations, such as poor photostability and insufficient organelle-targeting stability during photothermal therapy. In this work, we introduce an "aldehyde functionalization" strategy for simultaneously enhancing photostability and mitochondria-immobilization of near-infrared fluorophores for the first time. Based on the proposed strategy, representative near-infrared organic molecules, namely AF-Cy, were rationally designed and synthesized. Upon aldehyde modification, the AF-Cy dyes displayed both remarkable photostability and mitochondrial-targeting stability. The strong absorption in the near-infrared region confers the AF-Cy dyes with outstanding fluorescent/photoacoustic imaging and photothermal therapy capabilities. Finally, in vitro and in vivo studies revealed the enhanced performance in inhibiting the growth of breast tumors under NIR laser radiation, and these results suggested the strong potential of AF-Cy dyes as efficient multimodal imaging-guided photothermal therapy agents, further highlighting the value of this simple strategy in the design high performance near-infrared fluorophores for tumor theranostics.