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Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence.
Raut, Sangram; Garud, Ashwini; Nagarajan, Bhavani; Sabnis, Nirupama; Remaley, Alan; Fudala, Rafal; Gryczynski, Ignacy; Gryczynski, Zygmunt; Dzyuba, Sergei V; Borejdo, Julian; Lacko, Andras.
Affiliation
  • Raut S; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Garud A; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Nagarajan B; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Sabnis N; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Remaley A; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Fudala R; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Gryczynski I; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Gryczynski Z; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Dzyuba SV; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Borejdo J; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
  • Lacko A; Departments of Physiology and Anatomy (S.R., A.G., B.N., N.S., A.L.) and Microbiology, Immunology and Genetics (R.F., I.G., Z.G., J.B.), UNT Health Science Center, Fort Worth, Texas; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.); and Departments o
J Pharmacol Exp Ther ; 373(1): 113-121, 2020 04.
Article in En | MEDLINE | ID: mdl-31941718
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, FÓ§rster 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. SIGNIFICANCE STATEMENT: Although lipoproteins have been considered as effective drug delivery agents, none of these nanoformulations has entered clinical trials to date. A major challenge to advancing lipoprotein-based formulations to the clinic has been the availability of a cost-effective protein or peptide constituent, needed for the assembly of the drug/lipoprotein nanocomplexes. This report of a robust, spontaneously assembling drug transport system from a single component could provide the template for a superior, targeted drug delivery strategy for therapeutics of cancer and other diseases (Counsell and Pohland, 1982).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Spectrometry, Fluorescence / Drug Carriers / Biomimetic Materials / Nanoparticles / Lipoproteins, HDL Language: En Journal: J Pharmacol Exp Ther Year: 2020 Document type: Article Country of publication: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Spectrometry, Fluorescence / Drug Carriers / Biomimetic Materials / Nanoparticles / Lipoproteins, HDL Language: En Journal: J Pharmacol Exp Ther Year: 2020 Document type: Article Country of publication: United States