Lipid interactions of LAH4, a peptide with antimicrobial and nucleic acid transfection activities

The cationic amphipathic designer peptide LAH4 exhibits potent antimicrobial, nucleic acid transfection and cell penetration activities. Closely related derivatives have been developed to enhance viral transduction for gene therapeutic assays. LAH4 contains four histidines and, consequently, its overall charge and membrane topology in lipid bilayers are strongly pH dependent. In order to better understand the differential interactions of this amphipathic peptide with negatively-charged membranes its interactions, topologies, and penetration depth were investigated in the presence of lipid bilayers as a function of pH, buffer, phospholipid head group, and fatty acyl chain composition using a combination of oriented synchrotron radiation circular dichroism spectroscopy as well as oriented and non-oriented solid-state NMR spectroscopy. This combination of methods indicates that in the presence of lipids with phosphatidylglycerol head groups, the topological equilibria of LAH4 is shifted towards more in-plane configurations even at neutral pH. In contrast, a transmembrane alignment is promoted when LAH4 interacts with membranes made of dimyristoyl phospholipids rather than palmitoyl-oleoyl-phospholipids. Finally, the addition of citrate buffer favours LAH4 transmembrane alignments, even at low pH, probably by complex formation with the cationic charges of the peptide. In summary, this study has revealed that the membrane topology of this peptide is readily modulated by the environmental conditions

Porous Silicon Particles for Cancer Therapy and Bioimaging

Porous silicon (pSi) engineered by electrochemical etching of silicon has been explored as a drug delivery carrier with the aim of overcoming the limitations of traditional therapies and medical treatments. pSi is biodegradable, non-cytotoxic and has optoelectronic properties that make this platform material a unique candidate for developing biomaterials for drug delivery and theranostics therapies. pSi provides new opportunities to improve existing therapies in different areas, paving the way for developing advanced theranostic nanomedicines, incorporating payloads of therapeutics with imaging capabilities. However, despite these outstanding advances, more extensive in-vivo studies are needed to assess the feasibility and reliability of this technology for real clinical practice. In this Chapter, we present an updated overview about the recent therapeutic systems based on pSi, with a critical analysis on the problems and opportunities that this technology faces as well as highlighting the growing potential of pSi technolgy