Regulating Mitochondrial pH with Light and Implications for Chemoresistance.

Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent-induced apoptosis. A boron-dipyrromethene (BODIPY) chromophore-based triarylsulfonium photoacid generator (BD-PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD-PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD-PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD-PAG revealed a new strategy in chemoresistance suppression.

Mitochondria Penetrating Peptide-Conjugated TAMRA for Live-Cell Long-Term Tracking.

Mitochondria are essential targets for treatment of diseases with mitochondrial disorders such as diabetes, cancer, and cardiovascular and neurodegenerative diseases. Mitochondria penetrating peptides (MPPs) are composed of cationic and hydrophobic amino acids that can target and permeate the mitochondrial membrane. Herein, a novel d-argine-phenylalanine-d-argine-phenylalanine-d-argine-phenylalanine-NH2 (rFrFrF) was tagged with a rhodamine-based fluorescent chromophore (TAMRA). This probe (TAMRA-rFrFrF) exhibited advantageous properties for long-term mitochondria tracking as demonstrated by fluorescence microscopy. Cell viability assays and oxygen consumption rates indicate low cytotoxicity and high biocompatibility of the new contrast agent. Colocalization studies suggest that TAMRA-rFrFrF is a promising candidate for continuous mitochondrial tracking for up to 3 days.

Diagnosis and treatment of pancreatic metastases in 22 patients: a retrospective study.

BACKGROUND: Pancreatic metastases (PMs) are rare and lack of guidelines for diagnosis and treatments .The aim of this study is to explore the diagnosis, treatment, and prognosis of pancreatic metastases. METHODS: Twenty-two patients with pancreatic metastases who had been hospitalized at the First Affiliated Hospital of China Medical University from October 1980 to October 2012 were included in the present retrospective study. Seven patients had gastric cancer, five had colon cancer, two each had lung and liver cancer, and one each had bladder cancer, gallbladder cancer, breast cancer, nasopharyngeal cancer, renal cell carcinoma, and carcinoid. RESULTS: No specific syndrome or imageological change was found for the pancreatic metastases. The most common symptoms were abdominal pain and jaundice. Hypo-echoic lesions with well-defined margins were found on ultrasonic examinations, and low-density lesions with heterogeneous enhancement were identified in CT images. Nineteen of the 22 received treatment. Three of the 8 patients (34.1%) that had undergone operation experienced complications, but all patients recovered after conventional treatment. Follow-up studies were performed for 17 patients (77.3%), and the median survival time from the diagnosis of pancreatic metastases was 13.2 months (range, 2 to 68 months). Of the five patients who underwent radical resection, one was lost to follow-up, one died at fifteen months postoperation, and the other three are still alive and free from disease (disease-free survival ranging from five to thirty-three months from the diagnosis of the pancreatic metastases). CONCLUSION: Pancreatic metastases are rare lesions with no specific symptoms. Radical resection should be performed if possible; however, aggressive treatment should be performed for unresectable pancreatic metastases.

Nuclear mTOR Signaling Orchestrates Transcriptional Programs Underlying Cellular Growth and Metabolism.

mTOR is a central regulator of cell growth and metabolism in response to mitogenic and nutrient signals. Notably, mTOR is not only found in the cytoplasm but also in the nucleus. This review highlights direct involvement of nuclear mTOR in regulating transcription factors, orchestrating epigenetic modifications, and facilitating chromatin remodeling. These effects intricately modulate gene expression programs associated with growth and metabolic processes. Furthermore, the review underscores the importance of nuclear mTOR in mediating the interplay between metabolism and epigenetic modifications. By integrating its functions in nutrient signaling and gene expression related to growth and metabolism, nuclear mTOR emerges as a central hub governing cellular homeostasis, malignant transformation, and cancer progression. Better understanding of nuclear mTOR signaling has the potential to lead to novel therapies against cancer and other growth-related diseases.

Dye-Loaded Quatsomes Exhibiting FRET as Nanoprobes for Bioimaging.

Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present a type of FONs with outstanding photophysical and physicochemical properties in-line with the stringent requirements for biomedical applications. These FONs are based on quatsome (QS) nanovesicles containing a pair of fluorescent carbocyanine molecules that give rise to Förster resonance energy transfer (FRET). Structural homogeneity, high brightness, photostability, and high FRET efficiency make these FONs a promising class of optical bioprobes. Loaded QSs have been used for in vitro bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility to monitor the intracellular vesicle fate. Taken together, the proposed QSs loaded with a FRET pair constitute a promising platform for bioimaging and theranostics.

Photo-uncaging of BODIPY oxime ester for histone deacetylases induced apoptosis in tumor cells.

A new class of BODIPY-based oxime ester photo-uncaging group was designed to release carboxylic acids. The mechanism and kinetics of the photo-uncaging procedure were studied. Further, we constructed a photo-uncaging drug delivery system to release valproic acid (VPA), which can inhibit the histone deacetylases and induce apoptosis in tumor cells.