Lipoprotein-Related and Apolipoprotein-Mediated Delivery Systems for Drug Targeting and Imaging

Abstract

The integration of lipoprotein-related or apolipoprotein-targeted nanoparticles as pharmaceutical carriers opens new therapeutic and diagnostic avenues in nanomedicine. The concept is to exploit the intrinsic characteristics of lipoprotein particles as being the natural transporter of apolar lipids and fat in human circulation. Discrete lipoprotein assemblies and lipoprotein-based biomimetics offer a versatile nanoparticle platform that can be manipulated and tuned for specific medical applications. This article reviews the possibilities for constructing drug loaded, reconstituted or artificial lipoprotein particles. The advantages and limitations of lipoproteinbased delivery systems are critically evaluated and potential future challenges, especially concerning targeting specificity, concepts for lipoprotein rerouting and design of innovative lipoprotein mimetic particles using apolipoprotein sequences as targeting moieties are discussed. Finally, the review highlights potential medical applications for lipoprotein-based nanoparticle systems in the fields of cardiovascular research, cancer therapy, gene delivery and brain targeting focusing on representative examples from literature.

Fig. (1)

Major lipoprotein classes. Physical characteristics, average chemical composition and apolipoprotein content of different lipoprotein species.

Fig. (2)

Schematic diagram of lipoprotein metabolism (A) and an overview of reverse cholesterol transport (B).

Fig. (3)

LDL particles can be modified to act as natural endogenous nanoparticles for targeted drug delivery or multifunctional molecular imaging. Representative ways to modify LDL are schematically depicted. Modified with permission from [40] © 2012 Prassl and Laggner, licensee InTech.

Fig. (4)

Microfluidic reconstitution of HDL nanoparticles. A schematic depiction of a microfluidic platform that allows for a single-step and large scale production of HDL particles. Reconstituted discoidal HDL (µHDL); DiO-µHDL for fluorescence; [S]-µHDL statin loaded rHDL as therapeutics; Au-µHDL, FeO-µHDL and QD-µHDL spherical rHDL with nanocrystalline core of gold, ironoxide and quantum dots for CT imaging, MRI and fluorescence microscopy, respectively. Reprinted with permission from [103]; copyright 2013 American Chemical Society.

Fig. (5)

Biomimetic HDL particles for nucleic acid delivery. (1) An aqueous solution of gold nanoparticles (AuNPs) is mixed with apo-AI. (2) A mixture of phospholipids is then added to the surface of the AuNPs to form biomimetic HDL AuNPs. HDL AuNPS are purified by centrifugation and are resuspended in water. (3) Chol-DNA is added to purified HDL AuNPs and the chol-DNA-HDL-AuNP conjugates are purified by centrifugation and resuspended in buffer. Reprinted with permission from [125]; copyright 2011 American Chemical Society.