Abstract
Apolipoproteins are critical structural and functional components of lipoproteins, which are large supramolecular assemblies composed predominantly of lipids and proteins, and other biomolecules such as nucleic acids. A signature feature of apolipoproteins is the preponderance of amphipathic α-helical motifs that dictate their ability to make extensive non-covalent inter- or intra-molecular helix–helix interactions in lipid-free states or helix–lipid interactions with hydrophobic biomolecules in lipid-associated states. This review focuses on the latter ability of apolipoproteins, which has been capitalized on to reconstitute synthetic nanoscale binary/ternary lipoprotein complexes composed of apolipoproteins/peptides and lipids that mimic native high-density lipoproteins (HDLs) with the goal to transport drugs. It traces the historical development of our understanding of these nanostructures and how the cholesterol accepting property of HDL has been reconfigured to develop them as drug-loading platforms. The review provides the structural perspective of these platforms with different types of apolipoproteins and an overview of their synthesis. It also examines the cargo that have been loaded into the core for therapeutic and imaging purposes. Finally, it lays out the merits and challenges associated with apolipoprotein-based nanostructures with a future perspective calling for a need to develop “zip-code”-based delivery for therapeutic and diagnostic applications.
Highlights
Introduction and Historical PerspectiveLipoproteins are large lipid/protein complexes that have been nature’s simple and elegant solution to the problem of transporting lipophilic biomolecules in the aqueous environment of biological systems
They differ in their origin or site of synthesis, composition, and cargo, with chylomicrons originating in the intestines transporting dietary lipids, very low-density lipoprotein (VLDL) synthesized by the liver, intermediate density lipoprotein (IDL) and low-density lipoprotein (LDL) derived from VLDL, and high-density lipoproteins (HDLs) synthesized by macrophages, Nanomaterials 2020, 10, 906; doi:10.3390/nano10050906
The last four decades have witnessed a deeper understanding of apolipoprotein structure and function in lipid-free and lipid-associated states that has led to the appreciation and parallel development of synthetic lipoproteins for drug delivery and imaging
Summary
Lipoproteins are large lipid/protein complexes that have been nature’s simple and elegant solution to the problem of transporting lipophilic biomolecules in the aqueous environment of biological systems. From a structural perspective, lipoproteins are spherical complexes composed of a monolayer of amphipathic lipids and apolipoproteins (apo) that encapsulate a core of neutral or nonpolar lipids. There are several types of lipoproteins that may be classified based on their electrophoretic mobility or density: chylomicron, very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). They differ in their origin or site of synthesis, composition, and cargo, with chylomicrons originating in the intestines transporting dietary lipids, VLDL synthesized by the liver, IDL and LDL derived from VLDL, and HDL synthesized by macrophages, Nanomaterials 2020, 10, 906; doi:10.3390/nano10050906 www.mdpi.com/journal/nanomaterials. 2 2ofo3f 635 intestines transporting dietary lipids, VLDL synthesized by the liver, IDL and LDL derived from smVLalDl iLn,teasntidnesH, DanLd assytnrothceysteizse. dWhbeyremasaaclrlolpiphoapgreost,eisnms ainllgiennteersatlinheasv,eapnrdoviadsetrdogcyutiedsi.ngWphrienrceiapsleas,ll HliDpLopinropteairntsiciunlagre, nesepraelchiaalvlye tphreonvaidsceedngtupiadritnicglepsrtinhcaitpaleres,gHenDeLraitnedpadrutirciunlgart,heesbpieocgiaelnlyestihseofnaHsDceLnt (aplsaortircelfeesrtrhedat taoreagsepnreer-aβteHdDduLr)inhgavtheesberiovgeednaesims oofdHelDsLy(satelsmosreffoerrrtehde tdoeavseplorep-mβ eHnDt Lo)f haapvoe-bsaesrveded nasnompoadrteilclseyssatesmpslaftoforrtmhes fdoervterlaonpsmpoenrtt aonfdadpoel-ibvaesreydenxaongoenpoarutsicnleosnapsolpalra/tafmorpmhsipfaotrhtircamnsoploecrtulaensd sudcehlivaesrdyruexgosg, tehneoruaspenuotnicpaoglaern/atsm, flpahvipoantohiidcsm, imoleacguinlegs, asuncdhdaiasgdnrousgtsic, tmheorlaecpueluetsi.c agents, flavonoids, imaTghineg,coandcedpitagonf oesmticplmoyoilnecguliepso. protein particles for drug encapsulation emerged more than 3 decaTdhese acgoon,cwephtenofneamtupralollyyinogcculirproinpgrolitpeionprpoatretiincslews eforer idnrituiaglleynecmappsluoylaetdiotno etrmanesrgpeodrt mthoeraeptehuatnic anddecaddiaegsnaogsot,icwahgeennntsat[u1r].allIyn oecacrulyrrisntugdliipeos,pLroDteLinisowlaetreedinfritoimallyhuempanloypeladstmo atrwanasspodret-cthoereradpaenudtic suanbdstidtuiategdnowstiitch abgioemntos le[1c]u. leIns (ecaarlllyedstLuDdLiesa,nLcDhoLrsi)sowlaithedcofmropmarhaubmleapnolpalraistymaswCaEs (dfoer-ceoxraemd palned restuinbystlitourteodlewoyitlhgrboiuompso)letocuolbesta(icnarlleecdonLsDtiLtuatendchLoDrsL) [w2]it.hScoommepianrcaobrlpeoproatlaerditlyysaosmCoEtr(ofporiceaxgaemnptsle breeatriinnygl loornogl-ecohyalingraolkuypls)amtoinoebstatihnatreteconndstiotubtedprLoDtoLna[2te].dSionmaen iancciodripcoernavteirdonlymsoemntostruocphicasagtheantts fobuenardining llyosnogs-ocmhaeisn. aSlukbysleaqmueinnetlsy,thsyatnthenetdictophboesphrootloipniadtsedwinthaonr awcitdhioc uetnovtihroenr mlipeindtsswucehreausstehdat tofoguennderiantelyrseocsoonmsetist.uSteudbsHeqDuLen(trlHy,DsLyn) twhehtichprheossepmhboleipnidastiwveitHh DorLw(Fitihgouurteo1t)h.erTlhiproidusghwoeuret tuhsiesd retoviegwen, etrhaeteterremconrHstiDtuLtewdilHl DbeL u(rsHedDiLn)tewrchhicahngreeasbemlybwleitnhatsiyvnethHeDticL H(FDigLu,rnea1n)o. lTiphorporuogtheoinust- tohris apreovlipewop, rtohteinte-brmaserdHnDaLnowstirlul cbtuereuss.ed interchangeably with synthetic HDL, nanolipoproteins- or apolipoprotein-based nanostructures
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