Fabrication of CaCO3-Coated Vesicles by Biomineralization and Their Application as Carriers of Drug Delivery Systems

We fabricated CaCO3-coated vesicles as drug carriers that release their cargo under a weakly acidic condition. We designed and synthesized a peptide lipid containing the Val-His-Val-Glu-Val-Ser sequence as the hydrophilic part, and with two palmitoyl groups at the N-terminal as the anchor groups of the lipid bilayer membrane. Vesicles embedded with the peptide lipids were prepared. The CaCO3 coating of the vesicle surface was performed by the mineralization induced by the embedded peptide lipid. The peptide lipid produced the mineral source, CO32−, for CaCO3 mineralization through the hydrolysis of urea. We investigated the structure of the obtained CaCO3-coated vesicles using transmission electron microscopy (TEM). The vesicles retained the spherical shapes, even in vacuo. Furthermore, the vesicles had inner spaces that acted as the drug cargo, as observed by the TEM tomographic analysis. The thickness of the CaCO3 shell was estimated as ca. 20 nm. CaCO3-coated vesicles containing hydrophobic or hydrophilic drugs were prepared, and the drug release properties were examined under various pH conditions. The mineralized CaCO3 shell of the vesicle surface was dissolved under a weakly acidic condition, pH 6.0, such as in the neighborhood of cancer tissues. The degradation of the CaCO3 shell induced an effective release of the drugs. Such behavior suggests potential of the CaCO3-coated vesicles as carriers for cancer therapies.

A new "on-off-on" g-C3N4 nanosheets fluorescent sensor for 5-Br-PADAP and Co2+ under acidic condition

Scientists were still working on developing a "turn-on" fluorescence sensor for Co2+, especially in acidic solutions. A novel "on-off-on" fluorescence sensor based on g-C3N4 nanosheets was designed and prepared in...

pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition

Programmed cell death-ligand 1 (PD-L1)/PD-1 axis is critical for maintenance of immune homeostasis by limiting overactivation of effector T-cell responses. The impairment of PD-L1/PD-1 signals play an important role in the pathogenesis of inflammatory diseases, making this pathway an ideal target for novel therapeutics to induce immune tolerance. Given weakly acidic environment as a putative hallmark of inflammation, in this study we designed a new cargo by linking the ectodomain of murine PD-L1 to the N terminus of pHLIPs, a low pH-responding and membrane-insertion peptide, and demonstrated its potent immune-suppressive activity. Specifically, PD-L1-pHLIP spanned the cellular membrane and perfectly recognized its ligand PD-1 in acidic buffer. Immobile PD-L1-pHLIP actively inhibited T-cell proliferation and IFN-γ production. Importantly, soluble PD-L1-pHLIP retained its function to dampen T-cell responses under acidic condition instead of neutral aqueous solution. Overall, these data suggest that PD-L1-pHLIP has potentials to be a novel therapeutic avenue for T-cell-mediated inflammatory diseases.

Acid Tolerant Bacterium Bacillus Amyloliquefaciens MBNC Retains Biocontrol Efficiency Against Fungal Phytopathogens in Low pH

Soil pH conditions have important consequences for microbial community structure, their dynamics, ecosystem processes, and interactions with plants. Low soil pH affects the growth and functional activity of bacterial biocontrol agents which may experience a paradigm shift in their ability to act antagonistically against fungal phytopathogens. In this study, the antifungal activity of an acid tolerant soil bacterium Bacillus amyloliquefaciens MBNC was evaluated under low pH and compared to its activity in neutral pH conditions. Bacterial supernatant from three-day old culture grown in low pH conditions were more effective against fungal pathogens. B. amyloliquefaciens MBNC harboured genes involved in the synthesis of secondary metabolites of which surfactin homologues, with varying chain length (C11 – C15) were identified through High-Resolution Mass Spectroscopy. The pH of the medium influenced the production of these metabolites. Surfactin C15 was exclusive to the extract of pH 4.5; production of iturinA and surfactin C11 was detected only in pH 7.0 while, surfactin C12, C13 and C14 were detected in extracts of both the pH conditions. The secretion of phytohormones viz. Indole Acetic Acid (IAA) and Gibberellic Acid (GA) by B. amyloliquefaciens MBNC were detected in higher amount in neutral condition compared to acidic condition. Although, secretion of metabolites and phytohormones in B. amyloliquefaciens MBNC was influenced by the pH condition of the medium, the isolate retained its antagonistic efficiency against several fungal phyto-pathogens under acidic condition.