RT Journal Article SR Electronic T1 Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles, using Intrinsic Fluorescence JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.119.262899 DO 10.1124/jpet.119.262899 A1 Sangram G Raut A1 Ashwini Garud A1 Bhavani Nagarajan A1 Nirupama Sabnis A1 Alan Remaley A1 Rafal Fudala A1 Ignacy Gryczynski A1 Zygmunt Gryczynski A1 Sergei V Dzyuba A1 Julian Borejdo A1 Andras G Lacko YR 2020 UL http://jpet.aspetjournals.org/content/early/2020/01/15/jpet.119.262899.abstract AB Reconstituted HDL (rHDL) conjtaining apolipoprotein A1 (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nano-micellar structures, and its characterization via steady state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, Forster Resonance Energy Transfer (FRET), Dynamic Light Scattering (DLS), and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 (SR-B1) in this process.SIGNIFICANCE STATEMENT Lipoproteins have been considered as effective drug delivery agents for over forty years. Nevertheless, to date, none of the lipoprotein nano formulation has entered clinical trials. One of the major challenges to advancing lipoprotein based formulations to the clinic has been the availability of a cost effective protein or peptide component of these drug/lipoprotein complexes. In our view, this is th first description of a robust drug transport system, spontaneously assembled from a single component. The simplicity and the effectiveness of this patented formulation could be the answer to achieving superior targeted drug delivery, especially to cancer cells and tumors.