Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential

Native nanostructured lipoproteins such as low- and high-density lipoproteins (LDL and HDL) are powerful tools for the targeted delivery of drugs and imaging agents. While the cellular recognition of well-known HDL-based carriers occurs via interactions with an HDL receptor, the selective delivery a...

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Main Authors: Lin Di, Andrei Maiseyeu
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Drug Delivery
Subjects:
Online Access:http://dx.doi.org/10.1080/10717544.2021.1886199
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author Lin Di
Andrei Maiseyeu
author_facet Lin Di
Andrei Maiseyeu
author_sort Lin Di
collection DOAJ
description Native nanostructured lipoproteins such as low- and high-density lipoproteins (LDL and HDL) are powerful tools for the targeted delivery of drugs and imaging agents. While the cellular recognition of well-known HDL-based carriers occurs via interactions with an HDL receptor, the selective delivery and uptake of LDL particles by target cells are more complex. The most well-known mode of LDL-based delivery is via the interaction between apolipoprotein B (Apo-B) – the main protein of LDL – and the low-density lipoprotein receptor (LDLR). LDLR is expressed in the liver, adipocytes, and macrophages, and thus selectively delivers LDL carriers to these cells and tissues. Moreover, the elevated expression of LDLR in tumor cells indicates a role for LDL in the targeted delivery of chemotherapy drugs. In addition, chronic inflammation associated with hypercholesterolemia (i.e., high levels of endogenous LDL) can be abated by LDL carriers, which outcompete the deleterious oxidized LDL for uptake by macrophages. In this case, synthetic LDL nanocarriers act as ‘eat-me’ signals and exploit mechanisms of native LDL uptake for targeted drug delivery and imaging. Lastly, recent studies have shown that the delivery of LDL-based nanocarriers to macrophages via fluid-phase pinocytosis is a promising tool for atherosclerosis imaging. Hence, the present review summarizes the use of natural and synthetic LDL-based carriers for drug delivery and imaging and discusses various mechanisms of targeting.
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spelling doaj.art-5444de644dca4b8f8af8e5d4569572882022-12-21T23:42:43ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642021-01-0128140842110.1080/10717544.2021.18861991886199Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potentialLin Di0Andrei Maiseyeu1Cardiovascular Research Institute, School of Medicine, Case Western Reserve UniversityCardiovascular Research Institute, School of Medicine, Case Western Reserve UniversityNative nanostructured lipoproteins such as low- and high-density lipoproteins (LDL and HDL) are powerful tools for the targeted delivery of drugs and imaging agents. While the cellular recognition of well-known HDL-based carriers occurs via interactions with an HDL receptor, the selective delivery and uptake of LDL particles by target cells are more complex. The most well-known mode of LDL-based delivery is via the interaction between apolipoprotein B (Apo-B) – the main protein of LDL – and the low-density lipoprotein receptor (LDLR). LDLR is expressed in the liver, adipocytes, and macrophages, and thus selectively delivers LDL carriers to these cells and tissues. Moreover, the elevated expression of LDLR in tumor cells indicates a role for LDL in the targeted delivery of chemotherapy drugs. In addition, chronic inflammation associated with hypercholesterolemia (i.e., high levels of endogenous LDL) can be abated by LDL carriers, which outcompete the deleterious oxidized LDL for uptake by macrophages. In this case, synthetic LDL nanocarriers act as ‘eat-me’ signals and exploit mechanisms of native LDL uptake for targeted drug delivery and imaging. Lastly, recent studies have shown that the delivery of LDL-based nanocarriers to macrophages via fluid-phase pinocytosis is a promising tool for atherosclerosis imaging. Hence, the present review summarizes the use of natural and synthetic LDL-based carriers for drug delivery and imaging and discusses various mechanisms of targeting.http://dx.doi.org/10.1080/10717544.2021.1886199low-density lipoproteinseat-me signaloxidized lipoproteinsynthetic ldl mimicsmolecular imagingdrug delivery
spellingShingle Lin Di
Andrei Maiseyeu
Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
Drug Delivery
low-density lipoproteins
eat-me signal
oxidized lipoprotein
synthetic ldl mimics
molecular imaging
drug delivery
title Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
title_full Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
title_fullStr Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
title_full_unstemmed Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
title_short Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
title_sort low density lipoprotein nanomedicines mechanisms of targeting biology and theranostic potential
topic low-density lipoproteins
eat-me signal
oxidized lipoprotein
synthetic ldl mimics
molecular imaging
drug delivery
url http://dx.doi.org/10.1080/10717544.2021.1886199
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AT andreimaiseyeu lowdensitylipoproteinnanomedicinesmechanismsoftargetingbiologyandtheranosticpotential