A DNA and mitochondria dual-targeted photosensitizer for two-photon-excited bioimaging and photodynamic therapy
2022
Zhou, Yuping | Xia, Weikang | Liu, Zhuang | Ye, Sheng | Wang, Lei | Liu, Ruiyuan
Biological substrates and organelle multi-targeted photosensitizers for ultra-efficient cancer treatment through photodynamic therapy (PDT) are highly desirable. Herein, a multiple pyridinium-anchored photosensitizer containing the triphenylamine unit, TPA-2PI, has been designed and utilized for DNA and mitochondria dual-targeted two-photon-excited bioimaging and PDT. TPA-2PI possesses an ultrahigh ABDA consumption rate of 194.84 nmol min⁻¹ in PBS medium, and an ultralow IC₅₀ value of 0.108 μM upon white-light irradiation (80 mW cm⁻², 6 min). After irradiation, the abnormal mitochondria have been remarkable occurred in 4T1 cells and further induced cell apoptosis for the efficient PDT efficacy by TPA-2PI. Upon two-photon excitation (λₑₓ = 960 nm), the green fluorescence signal of DCFH-DA showed a dramatic turn-on effect. Furthermore, TPA-2PI could penetrate deeper cells (24 μm) and abdominal blood vessels (384 μm). The investigation of the TPA-2PI-triggered PDT effect in vivo further validated the efficacy of cancer cell ablation and significant inhibition of tumor growth. Moreover, the immunofluorescence staining results and blood biochemical parameters after treatment proved the bio-safety of TPA-2PI. The dual-targeted TPA-2PI can serve as a desirable photosensitizer for efficient cancer treatment, and this work sheds light on the development of biological substrate and organelle multi-targeted photosensitizers for future biological applications.
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