A mitochondria-targeted NIR fluorescent probe with pH-switchable viscosity response and photodynamic therapy via an O2‑independent photocatalyst

The tumor microenvironment in solid tumor is usually featured by low pH, high viscosity, and hypoxia etc. Real-time monitoring and efficient suppression of tumor tissues based on the characteristic parameters of the tumor site holds significant importance. Herein, we design a mitochondria-targeted NIR fluorescent probe named HX by incorporating naphthalene moiety with hemicyanine dyes. Under acidic conditions in tumor site, the neutral probe HX can be protonated with the pyranoid ring opening, thereby activating the donor-π-acceptor (D-π-A) framework and enhancing its sensitivity to changes in viscosity. In addition, the positive charge of the hemicyanine structure promotes the probe to enter into the mitochondria. Thus, HX has the ability of pH-switch to target mitochondria and detect the viscosity of the tumor acidic microenvironment. Furthermore, we also demonstrate that it can be served as photosensitizer with Type Ⅰ reaction for photodynamic therapy (PDT) in mitochondria. By using simulated tumor mice, we finally demonstrate that HX can distinguish tumor tissues from normal tissues in intraoperative navigation and monitor wound infection, as well as enhanced tumor inhibition with low concentration O₂.