Hypoxia activated fluorescent probe for specific visualization of mitochondrial dysfunction in tumor

Abstract

Selectively monitoring the mitochondrial dysfunction and viability of tumor was an important task for the treatment against cancer, which was helpful for controlling the appropriate radiotherapy and chemotherapy dose to minimize side-effect. However, tumor-specific fluorescent probes enabled the visualization of mitochondrial dysfunction in tumor tissues were rarely reported. Herein, a hypoxia-activated fluorescent probe (NTQ) was fabricated for selectively illuminating tumor and monitoring the mitochondrial dysfunction in tumor. NTQ was designed by linking nitrobenzene unit to a quinolinium moiety to form an "A-π-A" electronic structure. Under hypoxia condition, NTQ was reduced as ASQ with "D-π-A" electronic structure to give enhanced deep-red fluorescence. ASQ was designed with positive charge and high affinity to RNA, which targeted mitochondria in live cells and detected reversible changes in mitochondrial membrane potential by its relocation into the nucleolus. In this manner, NTQ enabled the selective visualization of tumor with hypoxia condition, and simultaneously reported the mitochondrial dysfunction in tumor. The probe revealed that increasing the oxidative stress under hypoxia can efficiently lead to tumor cells apoptosis, and traditional anti-tumor drugs including paclitaxel and colchicine can lead to tumor cell apoptosis under hypoxia condition. Particularly, the tumor tissues were selectively lighted up by NTQ, and mitochondrial dysfunction in tumor tissue was successfully detected with NTQ via its immigration from mitochondria to nucleolus.