Mitochondrial Protein Density, Biomass, and Bioenergetics as Predictors for the Efficacy of Glioma Treatments.

The metabolism of glioma cells exhibits significant heterogeneity and is partially responsible for treatment outcomes. Given this variability, we hypothesized that the effectiveness of treatments targeting various metabolic pathways depends on the bioenergetic profiles and mitochondrial status of glioma cells. To this end, we analyzed mitochondrial biomass, mitochondrial protein density, oxidative phosphorylation (OXPHOS), and glycolysis in a panel of eight glioma cell lines. Our findings revealed considerable variability: mitochondrial biomass varied by up to 3.2-fold, the density of mitochondrial proteins by up to 2.1-fold, and OXPHOS levels by up to 7.3-fold across the cell lines. Subsequently, we stratified glioma cell lines based on their mitochondrial status, OXPHOS, and bioenergetic fitness. Following this stratification, we utilized 16 compounds targeting key bioenergetic, mitochondrial, and related pathways to analyze the associations between induced changes in cell numbers, proliferation, and apoptosis with respect to their steady-state mitochondrial and bioenergetic metrics. Remarkably, a significant fraction of the treatments showed strong correlations with mitochondrial biomass and the density of mitochondrial proteins, suggesting that mitochondrial status may reflect glioma cell sensitivity to specific treatments. Overall, our results indicate that mitochondrial status and bioenergetics are linked to the efficacy of treatments targeting metabolic pathways in glioma

BIOENERGETICS OF COLORECTAL CANCER CELLS DEFINES THEIR SENSITIVITY TO THE PHARMACOLOGICAL TARGETING OF THE MITOCHONDRIAL ELECTRON TRANSPORT CHAIN

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PHARMACOLOGICAL INDUCTION OF MITOCHONDRIAL DYSFUNCTION IN TUMOR-ASSOCIATED MACROPHAGES AS A STRATEGY FOR CANCER THERAPY

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Multilayer Capsules of Bovine Serum Albumin and Tannic Acid for Controlled Release by Enzymatic Degradation

With the purpose to replace expensive and significantly cytotoxic positively charged polypeptides in biodegradable capsules formed via Layer-by-Layer (LbL) assembly, multilayers of bovine serum albumin (BSA) and tannic acid (TA) are obtained and employed for encapsulation and release of model drugs with different solubility in water: hydrophilic-tetramethylrhodamine-isothiocyanate-labeled BSA (TRITC-BSA) and hydrophobic 3,4,9,10-tetra-(hectoxy-carbonyl)-perylene (THCP). Hydrogen bonding is proposed to be predominant within thus formed BSA/TA films. The TRITC-BSA-loaded capsules comprising 6 bilayers of the protein and polyphenol are benchmarked against the shells composed of dextran sulfate (DS) and poly-l-arginine (PARG) on degradability by two proteolytic enzymes with different cleavage site specificity (i.e., α-chymotrypsin and trypsin) and toxicity for murine RAW264.7 macrophage cells. Capsules of both types possess low cytotoxicity taken at concentrations equal or below 50 capsules per cell, and evident susceptibility to α-chymotrypsin resulted in release of TRITC-BSA. While the BSA/TA-based capsules clearly display resistance to treatment with trypsin, the assemblies of DS/PARG extensively degrade. Successful encapsulation of THCP in the TRITC-BSA/TA/BSA multilayer is confirmed, and the release of the model drug is observed in response to treatment with α-chymotrypsin. The thickness, surface morphology, and enzyme-catalyzed degradation process of the BSA/TA-based films are investigated on a planar multilayer comprising 40 bilayers of the protein and polyphenol deposited on a silicon wafer. The developed BSA/TA-based capsules with a protease-specific degradation mechanism are proposed to find applications in personal care, pharmacology, and the development of drug delivery systems including those intravenous injectable and having site-specific release capability