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Review
. 2020:159:377-390.
doi: 10.1016/j.addr.2020.08.003. Epub 2020 Aug 11.

Lipoprotein-based drug delivery

Sara Busatto  1 , Sierra A Walker  2 , Whisper Grayson  3 , Anthony Pham  2 , Ming Tian  2 , Nicole Nesto  3 , Jacqueline Barklund  3 , Joy Wolfram  4
Affiliations
Review

Lipoprotein-based drug delivery

Sara Busatto et al. Adv Drug Deliv Rev. 2020.

Abstract

Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous lipids to target cells through cell membrane receptors or cell surface-bound lipoprotein lipase. The stability, biocompatibility, and selective transport of LPs make them promising delivery vehicles for various therapeutic and imaging agents. This review discusses isolation, manufacturing, and drug loading techniques used for LP-based drug delivery, as well as recent applications for diagnosis and treatment of cancer, atherosclerosis, and other life-threatening diseases.

Keywords: Biocompatible nanoparticles; Chemotherapy; Chylomicrons; Drug delivery; High-density lipoproteins; Low-density lipoproteins; Lymphatic transport; Purification; Synthetic lipoproteins; Very low-density lipoproteins.

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Figures

Fig. 1.
Fig. 1.. Examples of lipoprotein (LP) isolation methods.
LPs have been isolated from plasma, conditioned cell culture media (e.g., hepatocytes), and lipoaspirate using ultracentrifugation, size-exclusion chromatography, immune-based precipitation, or tangential flow filtration. EV, extracellular vesicle.
Fig. 2.
Fig. 2.. Example structure of synthetic LPs.
LPs can be synthesized in a laboratory setting combining synthetic/recombinant proteins, cholesterol, phospholipids, cholesterol esters, and triacylglycerols.
Fig. 3.
Fig. 3.. Examples of LP drug loading.
Various approaches can be used to load therapeutic or imaging agents in LPs, including passive loading or chemical conjugation, core loading or surface loading, and interactions with protein or lipids. In preclinical studies, engineered LPs have been used for various applications, including cancer treatment, gene therapy, atherosclerosis treatment, and imaging.
Fig. 4.
Fig. 4.. sHDL nanodisc-based cancer vaccine.
(A) Synthetic high-density lipoprotein (sHDL) nanodiscs are conjugated with antigen (Ag) peptides and cholesterol-modified immunostimulatory molecules (Cho-CpG) adjuvant. Ag peptides were modified with a cysteine-serine-serine (CSS) linker. (B) Following subcutaneous administration, the sHDL nanodiscs deliver Ag peptides and CpG to draining lymph nodes, promoting antigen presentation and dendritic cell (DC) maturation. This activates CD8+ T cell responses that target and kill cancer cells in peripheral tissues. Adapted from Kuai et al. [69] with permission. CD, cluster of differentiation. CTLA-4, cytotoxic T-lymphocyte-associated protein 4. MHC, major histocompatibility complex. PD-1, programmed cell death protein 1. TCR, T-cell receptor.
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