Probing the assembly of HDL mimetic, drug carrying nanoparticles using intrinsic fluorescences

Sangram Raut, Ashwini Garud, Bhavani Nagarajan, Nirupama Sabnis, Alan Remaley, Rafal Fudala, Ignacy Gryczynski, Zygmunt Gryczynski, Sergei V. Dzyuba, Julian Borejdo, Andras Lacko

Research output: Contribution to journalArticle

Abstract

Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (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 diseases, 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 nanomicellar 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, Förster resonance energy transfer (FRET), dynamic light scattering, 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 in this process.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume373
Issue number1
DOIs
StatePublished - 1 Apr 2020

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