Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential.
Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential.
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DOI：
10.1080/10717544.2021.1886199
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发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Maiseyeu A
中科院分区：
文献类型：
--
作者：
Di L;Maiseyeu A
天然纳米结构脂蛋白，如低密度脂蛋白和高密度脂蛋白（LDL和HDL）是靶向递送药物和显像剂的有力工具。虽然众所周知的基于HDL的载体的细胞识别通过与HDL受体的相互作用发生，但靶细胞对LDL颗粒的选择性递送和摄取更为复杂。最熟知的基于LDL的递送模式是通过载脂蛋白B（Apo-B）（LDL的主要蛋白）和低密度脂蛋白受体（LDLR）之间的相互作用。LDLR在肝脏、脂肪细胞和巨噬细胞中表达，因此选择性地将LDL载体递送至这些细胞和组织。此外，肿瘤细胞中LDLR的表达升高表明LDL在化疗药物的靶向递送中发挥作用。此外，与高胆固醇血症相关的慢性炎症（即，高水平的内源性LDL）可以通过LDL载体而减少，LDL载体竞争性地胜过有害的氧化LDL以被巨噬细胞摄取。在这种情况下，合成的LDL纳米载体充当“吃我”信号，并利用天然LDL摄取机制用于靶向药物递送和成像。最后，最近的研究表明，通过液相胞饮作用将基于LDL的纳米载体递送至巨噬细胞是用于动脉粥样硬化成像的有前途的工具。因此，本综述总结了使用天然和合成的LDL为基础的载体的药物输送和成像，并讨论了各种机制的目标。
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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DOI：
10.1590/1414-431x20177090
发表时间：
2018-01-23
期刊：
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子：
--
作者：
Freitas SCMP;Tavares ER;Silva BMO;Meneghini BC;Kalil-Filho R;Maranhão RC
通讯作者：
Maranhão RC
影响因子：
4.8
作者：
Cavigiolio, Giorgio;Geier, Ethan G.;Oda, Michael N.
通讯作者：
Oda, Michael N.
影响因子：
64.5
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
影响因子：
3.4
作者：
Daminelli, Elaine N.;Martinelli, Ana E. M.;Maranhao, Raul C.
通讯作者：
Maranhao, Raul C.
影响因子：
6.2
作者：
Poree, Dawanne E.;Zablocki, Kyle;Faig, Allison;Moghe, Prabhas V.;Uhrich, Kathryn E.
通讯作者：
Uhrich, Kathryn E.