ABSTRACT
Fluorescence-image guided surgery (FGS) can intraoperatively provide real-time visualization of a tumor incisal edge and high-resolution identification of tumor foci to improve treatment outcomes. In this contribution, we report a fluorescent probe NB-TAM based on intramolecularly folded photoinduced electron transfer (PET), which displayed a prominent turn-on response in the near-infrared (NIR) window upon specific interaction with the estrogen receptor (ER). Significantly, NB-TAM could delineate a clear tumor incisal edge (tumor-to-normal tissue ratio > 5) in a 70-min time window, and was successfully used to guide the facile and precise resection of ER+ breast tumors in mice. To our surprise, NB-TAM was found to be capable of identifying very tiny lung metastatic ER+ breast tumor foci (0.4 × 0.3 mm), and this ultrahigh resolution was essential to effectively promote tumor resection precision and early diagnosis of tiny tumors. These results clearly elucidate the promising application of NB-TAM as a diagnostic agent for intraoperative fluorescence imaging of ER+ breast cancer.
Subject(s)
Breast Neoplasms , Fluorescent Dyes , Optical Imaging , Receptors, Estrogen , Animals , Fluorescent Dyes/chemistry , Female , Breast Neoplasms/pathology , Breast Neoplasms/diagnostic imaging , Humans , Mice , Receptors, Estrogen/metabolism , Receptors, Estrogen/analysis , Mice, Inbred BALB C , Mice, NudeABSTRACT
Nucleic acids are mainly found in the mitochondria and nuclei of cells. Detecting nucleic acids in the mitochondrion and nucleus in cascade mode is crucial for understanding diverse biological processes. This study introduces a novel nucleic acid-based fluorescent styrene dye (SPP) that exhibits light-driven cascade migration from the mitochondrion to the nucleus. By introducing N-arylpyridine on one side of the styrene dye skeleton and a bis(2-ethylsulfanyl-ethy)-amino unit on the other side, we found that SPP exhibits excellent DNA specificity (16-fold, FDNA/Ffree) and a stronger binding force to nuclear DNA (-5.09 kcal/mol) than to mitochondrial DNA (-2.59 kcal/mol). SPP initially accumulates in the mitochondrion and then migrates to the nucleus within 10 s under light irradiation. By tracking the damage to nucleic acids in apoptotic cells, SPP allows the successful visualization of the differences between apoptosis and ferroptosis. Finally, a triphenylamine segment with photodynamic effects was incorporated into SPP to form a photosensitizer (MTPA-SPP), which targets the mitochondria for photosensitization and then migrates to the nucleus under light irradiation for enhanced photodynamic cancer cell treatment. This innovative nucleic acid-based fluorescent molecule with light-triggered mitochondrion-to-nucleus migration ability provides a feasible approach for the in situ identification of nucleic acids, monitoring of subcellular physiological events, and efficient photodynamic therapy.
Subject(s)
Cell Nucleus , Fluorescent Dyes , Light , Mitochondria , Optical Imaging , Humans , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/chemistry , Cell Nucleus/metabolism , Cell Nucleus/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , DNA/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , HeLa Cells , Apoptosis/drug effects , Photochemotherapy , Cell Line, Tumor , Neoplasms/diagnostic imagingABSTRACT
We synthesized and characterized three types of isostructural iodoargentates, [TM(phen)3]Ag2I4·3DMF (TM = Co (1), Ni (2), Zn (3)), [TM(phen)3]Ag3I5·DMF (TM = Co (4), Ni (5), Zn (6)), and [TM(phen)3]2Ag8I12·7DMF (TM = Co (7), Ni (8), Zn (9)) (phen = 1,10-phenanthroline, DMF = dimethylformamide) using transition-metal (TM) complexes as the structure-directing agents. Compounds 1-3 and compounds 4-6 feature zero-dimensional anionic [Ag4I8]4- and [Ag6I10]4- clusters, respectively. All of the [TM(phen)3]2+ cations in compounds 1-6 are arranged into a two-dimensional (2D) (6,3) net layer. Interestingly, compounds 1-3 are kinetically unstable in the mother solution, and they can be converted to compounds 4-6 via irreversible single-crystal to single-crystal transformation processes, respectively, with distinct changes in the crystal morphology and structure. Compounds 7-9 feature one-dimensional (1D) zigzag chains constructed from [Ag8I12]4- units. The UV-vis diffuse reflectance measurements demonstrate that compounds 1-9 possess the characteristics of semiconductors with band gaps of 2.58-2.71 eV and visible-light-irradiation-induced photocatalytic activities. Especially, compound 3 possesses higher photocatalytic degradation activity toward crystal violet (CV) and rhodamine B (RhB) in comparison to P25 under identical conditions. Moreover, the mechanism study reveals that the TM complex cations make a great contribution to the photocatalytic activity.