We use 2H NMR to study the effects of probes on the miscibility transition in multilamellar vesicles of di(18:1) phosphatidylcholine (PC; DOPC), chain perdeuterated di(16:0)PC (DPPCd62), and cholesterol both with and without 0.5 mol % of the fluorescent probes DiIC12 and DiOC18. Both probes raise the miscibility transition temperature in dispersions of 1:1 DOPC/DPPCd62 + 30% cholesterol but to differing extents. In membranes containing the popular probe DiIC12, the fraction of DPPCd62 lipids in the liquid disordered phase is increased, and the ordering of that phase is reduced even at low temperatures. All findings are consistent with a probe-induced expansion of the entire miscibility phase boundary. We examine membranes with smaller DiIC12 fractions and find a significant increase in transition temperature for samples with 0.05 mol % DiIC12, demonstrating that trace components can dramatically alter membrane phase behavior.
Most therapeutic agents suffer from poor solubility, rapid clearance from the blood stream, a lack of targeting, and often poor translocation ability across cell membranes. Drug/gene delivery systems (DDSs) are capable of overcoming some of these barriers to enhance delivery of drugs to their right place of action, e.g. inside cancer cells. In this review, we focus on nanoparticles as DDSs. Complementary experimental and computational studies have enhanced our understanding of the mechanism of action of nanocarriers and their underlying interactions with drugs, biomembranes and other biological molecules. We review key biophysical aspects of DDSs and discuss how computer modeling can assist in rational design of DDSs with improved and optimized properties. We summarize commonly used experimental techniques for the study of DDSs. Then we review computational studies for several major categories of nanocarriers, including dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, and carbon-based DDSs, and gold nanoparticles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
The distribution of ionizable amino lipids (KC2) is critical in structure of lipid nanoparticles, siRNA entrapment and endosomal release. Neutral KC2 segregates from phospholipids (POPC) and forms an oily core in the bilayer interior.
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