TY - JOUR
T1 - Probing the assembly of HDL mimetic, drug carrying nanoparticles using intrinsic fluorescences
AU - Raut, Sangram
AU - Garud, Ashwini
AU - Nagarajan, Bhavani
AU - Sabnis, Nirupama
AU - Remaley, Alan
AU - Fudala, Rafal
AU - Gryczynski, Ignacy
AU - Gryczynski, Zygmunt
AU - Dzyuba, Sergei V.
AU - Borejdo, Julian
AU - Lacko, Andras
N1 - Funding Information:
This research was supported by Cancer Prevention and Research Institute of Texas (DP150091), The Rutledge Cancer Foundation, Wheels for Wellness of Fort Worth, TX, to A.L. This work was also supported in part by Texas Alzheimer’s Research Care and Consortium (2018-48-51-JI) and Leukemia Texas Foundation grants to S.R. A.L. (University of North Texas Health Science Center), A.R. (National Institutes of Health) are joint contributors to the patent (US20150343069A1) on the Myr5A nanoparticles. No other conflicts are reported. https://doi.org/10.1124/jpet.119.262899. s This article has supplemental material available at jpet.aspetjournals.org.
Funding Information:
This research was supported by Cancer Prevention and Research Institute of Texas (DP150091), The Rutledge Cancer Foundation, Wheels for Wellness of Fort Worth, TX, to A.L. This work was also supported in part by Texas Alzheimer's Research Care and Consortium (2018-48-51-JI) and Leukemia Texas Foundation grants to S.R. A.L. (University of North Texas Health Science Center), A.R. (National Institutes of Health) are joint contributors to the patent (US20150343069A1) on the Myr5A nanoparticles. No other conflicts are reported.
Publisher Copyright:
Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85082147590&partnerID=8YFLogxK
U2 - 10.1124/jpet.119.262899
DO - 10.1124/jpet.119.262899
M3 - Article
C2 - 31941718
AN - SCOPUS:85082147590
SN - 0022-3565
VL - 373
SP - 113
EP - 121
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -