RESUMEN
Nuclei and mitochondria are the only cellular organelles containing genes, which are specific targets for efficient cancer therapy. So far, several photosensitizers have been reported for mitochondria targeting, and another few have been reported for nuclei targeting. However, none have been reported for photosensitization in both mitochondria and nucleus, especially in cascade mode, which can significantly reduce the photosensitizers needed for maximal treatment effect. Herein, a light-driven, mitochondria-to-nucleus cascade dual organelle cancer cell ablation strategy is reported. A functionalized iridium complex, named BT-Ir, is designed as a photosensitizer, which targets mitochondria first for photosensitization and subsequently is translocated to a cell nucleus for continuous photodynamic cancer cell ablation. This strategy opens new opportunities for efficient photodynamic therapy.
Asunto(s)
Núcleo Celular/efectos de los fármacos , Iridio/farmacología , Mitocondrias/efectos de los fármacos , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Técnicas de Ablación/métodos , Línea Celular Tumoral , HumanosRESUMEN
The unbalanced metabolism of sulfur dioxide can cause various diseases, such as neurological disorders and lung cancer. Until now, some researches revealed that the normal function of lysosomes would be disrupted by its abnormal viscosity. As a signal molecule, sulfur dioxide (SO2) plays an important role in lysosome metabolism. However, the connection of metabolism between the SO2 and viscosity in lysosomes is still unknown. Herein, we developed a benzothiazole-based near-infrared (NIR) fluorescent probe (Triph-SZ), which can monitor the SO2 derivatives and respond to the change of viscosity in lysosomes through two-photon imaging. Triph-SZ present high sensitivity and selectivity fluorescence response with the addition of SO2 derivatives based on the nucleophilic addition, and it also exhibits a sensitive fluorescence enhancement to environmental viscosity, which allows Triph-SZ to be employed to monitor the level of HSO3- and viscosity changes in lysosomes by the two-photon fluorescence lifetime imaging microscopy.
Asunto(s)
Benzotiazoles , Colorantes Fluorescentes , Células HeLa , Humanos , Microscopía Fluorescente , Dióxido de Azufre , ViscosidadRESUMEN
The misregulation of nucleic acids behavior leads to cell dysfunction and induces serious diseases. A ratiometric fluorescence probe is a powerful tool to study the dynamic behavior and function relationships of nucleic acids. However, currently, no such effective probe has been reported for in situ, real-time tracking of nucleic acids in living cells and tissue sections. Herein, the unique probe named QPP-AS was rationally designed for ratiometric fluorescence response to nucleic acids through skillful regulation of the intramolecular charge-transfer capabilities of the electron acceptor and donor. Encouraged by the advantages of the selective nucleic acid response, ideal biocompatibility, and high signal-to-noise ratio, QPP-AS has been applied for in situ, real-time ratiometric fluorescence imaging of nucleic acids in living cells for the first time. Furthermore, we have demonstrated that QPP-AS is capable of visualizing the dynamic behavior of nucleic acids during different cellular processes (e.g., cell division and apoptosis) by ratiometric fluorescence imaging. More significantly, QPP-AS has been successfully used for ratiometric fluorescence imaging of nucleic acids in human tissue sections, which provides not only the cell contour, nuclear morphology, and nuclear-plasma ratio but also the nucleic acid content information and may greatly improve accuracy in clinicopathological diagnosis.