Cationic lipid

Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism...

Rationale: Microbubble ( MB ) contrast agents combined with ultrasound targeted microbubble cavitation ( UTMC ) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor ( EGFR ), to squamous cell carcinoma ( SCC ) via a novel MB-liposome complex ( LPX ). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4 F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction...

Supported lipid bilayers (SLBs), two-dimensional lipid films formed on a solid-supporting substrate, serve as models for biomembranes and exhibit remarkable potential in chemistry, biology, and medicine. However, preparing SLBs with highly negatively charged contents on the negatively charged surface by overcoming electrostatic repulsion remains a challenge. Here, a creative bicelle-mediated and divalent cation-free SLB preparation method with the assistance of phosphate-buffered saline (PBS) solution was proposed, which can form the SLBs containing 50% DOPS or 30% CL on the silica surface monitored by a quartz crystal microbalance with dissipation (QCM-D)...

ABSTACTThe medicinal properties of genetic drugs are highly dependent on the design of delivery systems. Ionizable cationic lipids are considered core materials in delivery systems. However, there has not yet been a widespread consensus on the relationship between the wide diversity of lipid structure design and gene delivery efficiency. The aims of the research work were to synthesize ionizable cholesterol derivatives (iChol-lipids) and to evaluate their potential applications as gene delivery vector. A series of iChol-lipids with different head groups were synthesized with carbamate bond spacer...

PURPOSE: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lingering threat to public health has fueled the search for effective therapeutics to treat SARS-CoV-2. This study aimed to develop lipid nanoparticle (LNP) inhibitors of SARS-CoV-2 entry to reduce viral infection in the nose and upper airway. METHODS: Two types of LNP formulations were prepared following a microfluidic mixing method. The LNP-Trap consisted of DOPC, DSPC, cholesterol, and DSPE-PEG-COOH modified with various spike protein binding ligands, including ACE2 peptide, recombinant human ACE2 (rhACE2) or monoclonal antibody to spike protein (mAb)...

The outer bacterial membrane of drug-resistant bacteria is a significant barrier to many antimicrobials. Therefore, the development of new antibacterials primarily focuses on damaging the outer bacterial membrane of Gram-negative bacteria. Among many membrane-disrupting substances, the most promising are cationic dendritic systems. However, the mode of action may vary among different strains due to variations in the lipid compositions of the membrane. Here, we investigated the interaction of two types of cationic imidazolium carbosilane dendrimers: one with a single cationic group (methyl imidazolium) and the other with the same cationic group but attached to a functional group (a pendant pyridyl moiety), capable of establishing interactions with membranes through H-bonding or ion-dipole electrostatic interactions...

Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disorder. The inflammation induced by cerebral hemorrhage plays a crucial role in the secondary injury of ICH and often accompanied by a poor prognosis, leading to disease exacerbation. However, blood-brain barrier (BBB) limiting the penetration of therapeutic drugs to the brain. In this paper, our primary objective is to develop an innovative, non-invasive, safe, and targeted formulation. This novel approach aims to synergistically harness the combined therapeutic effects of drugs to intervene in inflammation via a non-injectable route, thereby significantly mitigating the secondary damage precipitated by inflammation following ICH...

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations...

In this study, we synthesized a family of novel ionic liquids (ILs) with meglumine (MGM) as cations and tartaric acid (TA), azelaic acid (AA), geranic acid (GA), and capric acid (CPA) as anions, using pharmaceutical additives via simple acid-base neutralization reactions. The successful synthesis was validated by attenuated total reflection-Fourier transform infrared (ATR-FTIR) and powder X-ray diffraction (PXRD). Thermal analysis using differential scanning calorimetry confirmed the glass transition temperature of MGM-ILs to be within the range of -43...

Capitellacin is the β-hairpin membrane-active cationic antimicrobial peptide from the marine polychaeta Capitella teleta . Capitellacin exhibits antibacterial activity, including against drug-resistant strains. To gain insight into the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment of dodecylphosphocholine (DPC) micelles using high-resolution NMR spectroscopy. In DPC solution, two structural forms of capitellacin were observed: a monomeric β-hairpin was in equilibrium with a dimer formed by the antiparallel association of the N -terminal β-strands and stabilized by intermonomer hydrogen bonds and Van der Waals interactions...

Mitochondria are most likely descendants of strictly aerobic prokaryotes from the class Alphaproteobacteria . The mitochondrial matrix is surrounded by two membranes according to its relationship with Gram-negative bacteria. Similar to the bacterial outer membrane, the mitochondrial outer membrane acts as a molecular sieve because it also contains diffusion pores. However, it is more actively involved in mitochondrial metabolism because it plays a functional role, whereas the bacterial outer membrane has only passive sieving properties...

Mechanosensation is a fundamental function through which cells sense mechanical stimuli by initiating intracellular ion currents. Ion channels play a pivotal role in this process by orchestrating a cascade of events leading to the activation of downstream signaling pathways in response to particular stimuli. Piezo1 is a cation channel that reacts with Ca2+ influx in response to pressure sensation evoked by tension on the cell lipid membrane, originating from cell-cell, cell-matrix, or hydrostatic pressure forces, such as laminar flow and shear stress...

In the 1990s, the identification of a non-selective ion channel, especially responsive to capsaicin, revolutionized the studies of somatosensation and pain that were to follow. The TRPV1 channel is expressed mainly in neuronal cells, more specifically, in sensory neurons responsible for the perception of noxious stimuli. However, its presence has also been detected in other non-neuronal cells, such as immune cells, β- pancreatic cells, muscle cells and adipocytes. Activation of the channel occurs in response to a wide range of stimuli, such as noxious heat, low pH, gasses, toxins, endocannabinoids, lipid-derived endovanilloid, and chemical agents, such as capsaicin and resiniferatoxin...

The recently developed mRNA-based coronavirus SARS-CoV-2 vaccines highlighted the great therapeutic potential of the mRNA technology. Although the lipid nanoparticles used for the delivery of the mRNA are very efficient, they showed, in some cases, the induction of side effects as well as the production of antibodies directed against particle components. Thus, the development of alternative delivery systems is of great interest in the pursuit of more effective mRNA treatments. In the present work, we evaluated the mRNA transfection capacities of a series of cationic histidine-rich amphipathic peptides derived from LAH4...

A variety of equilibrium and non-equilibrium methods have been used in a multidisciplinary approach to study the conformational landscape associated with the binding of different cations to the pore of potassium channels. These binding processes, and the conformational changes resulting therefrom, modulate the functional properties of such integral membrane properties, revealing these permeant and blocking cations as true effectors of such integral membrane proteins. KcsA, a prototypic K+ channel from Streptomyces lividans, has been extensively characterized in this regard...

The use of an exogenous pulmonary surfactant (EPS) to deliver other relevant drugs to the lungs is a promising strategy for combined therapy. We evaluated the interaction of polymyxin B (PxB) with a clinically used EPS, the poractant alfa Curosurf (PSUR). The effect of PxB on the protein-free model system (MS) composed of four phospholipids (diC16:0PC/16:0-18:1PC/16:0-18:2PC/16:0-18:1PG) was examined in parallel to distinguish the specificity of the composition of PSUR. We used several experimental techniques (differential scanning calorimetry, small- and wide-angle X-ray scattering, small-angle neutron scattering, fluorescence spectroscopy, and electrophoretic light scattering) to characterize the binding of PxB to both EPS...

The inability to systemic administration of nanoparticles, particularly cationic nanoparticles, has been a significant barrier to their clinical translation due to toxicity concerns. Understanding the in vivo behavior of cationic lipids is crucial, given their potential impact on critical biological components such as immune cells and hematopoietic stem cells (HSC). These cells are essential for maintaining the body's homeostasis, and their interaction with cationic lipids is a key factor in determining the safety and efficacy of these nanoparticles...

The involvement of the TRP vanilloid 1 (TRPV1) cation channel on the 5-Fluorouracil (5-FU)-caused Ca2+ signals through the activation of the apoptotic signaling pathway and stimulating the mitochondrial Ca2+ and Zn2+ accumulation-induced reactive oxygen species (ROS) productions in several cancer cells, except the colorectal cancer (HT-29) cell line, was recently reported. I aimed to investigate the action of silver nanoparticles (SiNPs) and 5-FU incubations through the activation of TRPV1 on ROS, apoptosis, and cell death in the HT-29 cell line...

The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake...

Mitochondrial uncouplers are actively sought as potential therapeutics. Here, we report the first successful synthesis of mitochondria-targeted derivatives of the highly potent uncoupler 3,5-di tert -butyl-4-hydroxybenzylidene-malononitrile (SF6847), bearing a cationic alkyl(triphenyl)phosphonium (TPP) group. As a key step of the synthesis, we used condensation of a ketophenol with malononitrile via the Knoevenagel reaction. SF-C5 -TPP with a pentamethylene linker between SF6847 and TPP, stimulating respiration and collapsing membrane potential of rat liver mitochondria at submicromolar concentrations, proved to be the most effective uncoupler of the series...