HDL drug carriers for targeted therapy.
Plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are strongly and inversely associated with cardiovascular risk. HDL is not a simple lipid transporter, but possesses multiple anti-atherosclerosis activities because it contains special proteins, signaling lipid, and microRNAs. Natural or recombinant HDLs have emerged as potential carriers for delivering a drug to a specified target. However, HDL function also depends on enzymes that alter its structure and composition, as well as cellular receptors and membrane micro-domains that facilitate interactions with the microenvironment. In this review, four mechanisms predicted to enhance functions or targeted therapy of HDL in vivo are discussed. The first involves caveolae-mediated recruitment of HDL signal to bind their receptors. The second involves scavenger receptor class B type I (SR-BI) mediating anchoring and fluidity for signal-lipid of HDL. The third involves lecithin-cholesterol acyltransferase (LCAT) concentrating the signaling lipid at the surface of the HDL particle. The fourth involves microRNAs (miRNAs) being delivered in the blood to special targets by HDL. Exploitation of these four mechanisms will promote HDL to carry targeted drugs and increase HDL's clinical value.
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, China. liuxing0626@163.com
Xing
X
Liu
Rong
R
Suo
Sheng-Lin
SL
Xiong
Qing-Hai
QH
Zhang
Guang-Hui
GH
Yi
D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism; D008076:Cholesterol, HDL / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D015507:Drugs, Investigational / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D055553:Prescription Drugs / Q000378:metabolism / Q000494:pharmacology; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D015398:Signal Transduction
D008076:Cholesterol, HDL; D004337:Drug Carriers; D015507:Drugs, Investigational; D008075:Lipoproteins, HDL; D035683:MicroRNAs; D055553:Prescription Drugs; D018110:Receptors, Lipoprotein; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; D007862:Phosphatidylcholine-Sterol O-Acyltransferase