Ahmed Mohammed Ali Abdulkhaleq,Yixu Zhao,Kun Qian,Xueshi Wang,Zhongfu Zuo,Xibin Zhou
Peroxynitrite (ONOO − ), a highly reactive nitrogen and oxygen species (RNS/ROS), has been associated with a numerous of pathophysiological diseases, including inflammation, cancer, neurodegenerative, and cardiovascular diseases. There are great demands to develop strategies that can detect ONOO − in biological systems. Herein, we developed a novel fluorescent probe based on carbon dots (CDs) for a very sensitive and selective detection and imaging of endogenous and exogenous ONOO − in cells and animal models. Green light-emitting (527 nm) CDs with high quantum yield (QY) was synthesized by hydrothermal method using resorcinol as carbon source. After the phenolic hydroxyl groups of the CDs are combined with the recognition group of ONOO − via covalent ether bond, the fluorescence is quenched and forming the fluorescent probe. Upon the addition of ONOO − to the probe, the ether bond has broken and the CDs fluorescence has recovered. This response has been detailed investigated, including response time, pH values, selectivity and sensitivity, and linearity range, which confirmed the satisfactory detection ability for ONOO − . The probe shows low cytotoxicity and was successfully applied for imaging of ONOO − exogenously and endogenously in cells and in live models of zebrafish and mice.
Due to biological safety and negligible toxicity, nitric oxide (NO) therapy has gained increasing interest in the field of cancer therapy during the past few years. However, individual NO cancer therapy normally exhibited limited therapeutic efficiency. In order to acquire satisfactory therapeutic outcomes, the NO therapy is usually combined with other therapeutic treatments, mostly chemotherapy. Herein, we constructed HA-TPP@NORM nanoparticles based on the co-assembly of an NO donor (NORM) and tetraphenylporphyrin (TPP)-modified hyaluronic acid, which can efficiently generate a highly biocidal molecule of peroxynitrite (ONOO−) via the synergistic interactions of the nitric oxide (NO) therapy and photodynamic therapy (PDT) to enhance the cancer therapeutic efficiency. In addition, MTT results exhibited that without light irradiation, the HA-TPP@NORM nanoparticles have favourable biocompatibility with the cell viability above 95% at the maximum TPP concentration (20 μg mL−1). Under simultaneous irradiation with 365 nm and 650 nm light, ONOO− can be efficiently produced in cancer cells via the direct coupling reaction of the generated NO and superoxide anion radical (O2˙−), which significantly enhanced the anticancer effect, when compared with individual NO therapy or PDT therapy. Therefore, the HA-TPP@NORM nanoparticles may provide a new insight into the design of efficiently NO-related cancer therapeutic systems.
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