Antibody‐Targeted Drug Delivery to Injured Arteries Using Layered Double Hydroxide Nanoparticles

Abstract

Targeted local delivery of a nanoparticle-based, antibody-targeted, and low molecular weight heparin (LMWH) delivery system successfully reduces restenosis and thrombus formation in an animal model. An antibody recognizing cross-linked fibrin (XLF) D-dimer is successfully conjugated to layered double hydroxide nanoparticles. Use of the anti-XLF-conjugated LMWH-carrying layered double hydroxide nanoparticles shows successful targeting of the nanoparticles (red) to the injured artery wall (green), resulting in decreased neointimal thickening and thrombus formation.

Hierarchical layered double hydroxide nanocomposites: structure, synthesis and applications

“…118 In the case of LDH nanocarriers, recent progress in targeting moiety design has been seen in conjugating folic acid and antibody agents. 20,57,[119][120][121] Folic acid has a high affinity (K d E 100 pM) for folate receptors which are often overexpressed in various human cancers, such as ovary, lung, kidney, colon cancer, etc.…”

Restenosis Treatments Using Nanoparticle-based Drug Delivery Systems

“…We further showed that this antibody effectively targeted LDH nanoparticles to the site of arterial injury, and that the sustained release of LMWH from the nanoparticles inhibited neointimal formation and thrombus development in a rat model of arterial injury [97]. .…”

Targeted Treatments for Restenosis and Vein Graft Disease

“…Antibodies recognising fibrin have been conjugated to a number of potential therapies, to target the drugs to the site of fibrin formation, that is, the site of injury. Various antibody-drug therapies have been shown to reduce thrombosis, neointimal formation and vessel remodelling, as well as improving reendothelialization in the vessel [102,[104][105][106][107]131].…”

“…Nanoparticles are 1-100 nm in size, with a large surface area, and often have magnetic and fluorescent properties [131,134,135,142] be better protected from degradation, making them available for longer periods and enhancing their therapeutic effects. This is a particular advantage for hydrophilic drugs, which are otherwise readily lost.…”

“…These include organic liposomes, polymers, and perfluorocarbon nanoparticles and inorganic nanoparticles such as layered double hydroxides (LDHs), magnetic nanoparticles, and titanium oxide (TiO 2 ). For example, liposomes incorporating antirestenotic drugs have been used to coat metallic stents and shown to function as a drug carrier in small animals [143][144][145], while LDH has been used to increase the amount of drug delivered in fibrin/antibody-targeted therapy [131].…”