ABSTRACT
Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O2⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO‒) generated from the co-existence of NO and O2⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.
ABSTRACT
Nanogenerator (triboelectric nanogenerator and piezoelectric nanogenerator) has experienced a rapid development since it was proposed. This technique can covert various mechanical energies into electric energy, including human motion energy, wind energy, acoustic energy and ocean energy. The converted electricity can be used for health monitoring and physiological function regulation, such as pulse detection, bioelectrical stimulation and cardiac pacing. This review summarizes the structure, working mechanism, output performance of nanogenerator and its latest progress in circulatory system, nervous system, biological tissue, sleep and rescue system. Additionally, a further analysis was also made on the application challenge of nanogenerator in clinical treatment. In the future, nanogenerator is expected to be an auxiliary power source, or even to replace battery to power medical electronic device and realize the self-powered health monitoring and physiological function regulation of human body.