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Instruments / Technical Area	Publication Details	Published
I22-Small angle scattering & Diffraction	Multifunctional nano‐biointerfaces: cytocompatible antimicrobial nanocarriers from stabilizer‐free cubosomes Mahsa Zabara , Berna Senturk , Mark Gontsarik , Qun Ren , Markus Rottmar , Katharina Maniura‐weber , Raffaele Mezzenga , Sreenath Bolisetty , Stefan Salentinig Advanced Functional Materials 2 DOI: 10.1002/adfm.201904007 Show Abstract ▼ Abstract: The rational design of alternative antimicrobial materials with reduced toxicity toward mammalian cells is highly desired due to the growing occurrence of bacteria resistant to conventional antibiotics. A promising approach is the design of lipid‐based antimicrobial nanocarriers. However, most of the commonly used polymer‐stabilized nanocarriers are cytotoxic. Herein, the design of a novel, stabilizer‐free nanocarrier for the human cathelicidin derived antimicrobial peptide LL‐37 that is cytocompatible and promotes cell proliferation for improved wound healing is reported. The nanocarrier is formed through the spontaneous integration of LL‐37 into novel, stabilizer‐free glycerol mono‐oleate (GMO)‐based cubosomes. Transformations in the internal structure of the cubosomes from Pn3m to Im3m‐type and eventually their transition into small vesicles and spherical micelles are demonstrated upon the encapsulation of LL‐37 into their internal bicontinuous cubic structure using small angle X‐ray scattering, cryogenic transmission electron microscopy, and light scattering techniques. Additional in vitro biological assays show the antimicrobial activity of the stabilizer‐free nano‐objects on a variety of bacteria strains, their cytocompatibility, and cell‐proliferation enhancing effect. The results outline a promising strategy for the comprehensive design of antimicrobial, cytocompatible lipid nanocarriers for the protection and delivery of bioactive molecules with potential for application as advanced wound healing materials.	Jul 2019
I22-Small angle scattering & Diffraction	From structure to function: pH-switchable antimicrobial nano-self-assemblies Mark Gontsarik , Anan Yaghmur , Qun Ren , Katharina Maniura-Weber , Stefan Salentinig Acs Applied Materials & Interfaces DOI: 10.1021/acsami.8b18618 Diamond Proposal Number(s): [17191] Show Abstract ▼ Abstract: Stimuli-responsive nanocarriers based on lipid self-assemblies have the potential to provide targeted delivery of antimicrobial peptides, limiting their side effects while protecting them from degradation in the biological environments. In the present study, we design and characterize a simple pH-responsive antimicrobial nanomaterial, formed through the self-assembly of oleic acid (OA) with the human cathelicidin LL-37 as model for an amphiphilic antimicrobial peptide. Colloidal transformations from core-shell cylindrical micelles with a cross-section diameter of ~ 5.5 nm and a length of ~ 23 nm at pH 7.0, to aggregates of branched thread-like micelles at pH 5.0 were detected using synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. Biological in vitro assays using an Escherichia coli bacteria strain showed high antimicrobial activity of the positively charged LL-37/OA aggregates at pH 5.0, which was not caused by the pH conditions themselves. Contrary to that, negligible antimicrobial activity was observed at pH 7.0 for the negatively charged cylindrical micelles. The nanocarrier’s ability to switch its biological activity ‘on’ and ‘off’ in response to changes in pH could be used to focus the antimicrobial peptides’ action to areas of specific pH in the body. The presented findings contribute to the fundamental understanding of lipid-peptide self-assembly, and may open up a promising strategy for designing simple pH-responsive delivery systems for antimicrobial peptides.	Dec 2018
I22-Small angle scattering & Diffraction	Temperature triggering of kinetically trapped self-assemblies in citrem-phospholipid nanoparticles Rama Prajapati , Stefan Salentinig , Anan Yaghmur Chemistry And Physics Of Lipids 216, 30 - 38 DOI: 10.1016/j.chemphyslip.2018.09.003 Diamond Proposal Number(s): [17191] Show Abstract ▼ Abstract: Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles are attractive nanocarriers for drug delivery, particularly for the solubilization of poorly water-soluble drugs. Due to the reported problems of complement activation and cytotoxicity of most investigated Pluronic F127-stabilized cubosomes and hexosomes, there is an interest in introducing safe stabilizers for these LLC nanodispersions. Citrem appears to be the stabilizer of choice for the colloidal stabilization of these LLC nano-self-assemblies owing to its hemocompatiblity and poor activation of the complement system. This anionic food-grade emulsifier in combination with soy phosphatidylcholine (SPC) can be used to introduce a library of hemocompatible lamellar and non-lamellar liquid crystalline nanodispersions at different lipid compositions. We found that batch-to-batch variability in citrem composition is associated with slight alterations in the size, structural characteristics, and surface charge of the produced citrem/SPC nanoparticles. Further, we report on the temperature-triggered alterations in these nano-self-assemblies at different lipid compositions by using synchrotron small angle X-ray scattering (SAXS). The addition of citrem at different temperatures induces lamellar to non-lamellar structural transitions as evident from the appearance of inverse bicontinuous cubic Pn3m and discontinuous hexagonal (H2) phases, respectively, upon increasing citrem concentration and varying temperature in the range of 5–59 °C. Citrem/SPC nanoparticles are attractive for use in the development of nanocarriers for drug delivery owing to their structural tunability and hemocompatiblity.	Nov 2018

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