High-Density Lipoprotein Nanobiologics for Precision Medicine

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Lipid Metabolism

Background:

• Nature inspires biomedical engineering, with nanotechnological approaches derived from biological concepts like viruses and exosomes.
• Lipoproteins, such as high-density lipoprotein (HDL), are natural nanostructures crucial for lipid transport, cell function, and disease.
• HDL's endogenous nature, small size (10 nm), and composition (apolipoprotein A1 and phospholipids) make it an ideal nanocarrier for inflammatory diseases.

Purpose of the Study:

• To provide an overview of methods for apolipoprotein A1 (apoA-I) extraction, isolation, purification, and recombinant production from native HDL.
• To discuss the reconstitution of HDL into nanobiologics (rHDL) and other HDL-derived platforms using innovative production methods.
• To highlight the diagnostic and therapeutic applications of HDL nanobiologics, including their specificity for inflammatory myeloid cells and in vivo studies.

Main Methods:

• Extraction, isolation, and purification of apoA-I from native HDL and recombinant production.
• Reconstitution of HDL (rHDL) and other HDL-derived nanobiologics using microfluidic-based production.
• Integration of imaging labels (radioisotopes, paramagnetic, fluorescent lipids) and therapeutic payloads (drugs, nanocrystals) into HDL nanobiologics.

Main Results:

• HDL nanobiologics are biocompatible, biodegradable, cross biological barriers, and interact with immune cells via receptors like ABCA1, ABCG1, and SR-BI.
• Functionalized HDL nanobiologics demonstrated utility in cardiovascular disease and cancer models via MRI, CT, and PET imaging.
• Successful translation of zirconium-89 radiolabeled HDL (89Zr-HDL) PET imaging from animal models to human cardiovascular disease patients.

Conclusions:

• Repurposed HDL nanobiologics offer a versatile platform for targeted diagnostics and therapeutics in inflammatory diseases and cancer.
• The development of HDL mimetics leverages nature-inspired designs for enhanced biocompatibility and efficacy.
• Further advances in nanobiologic-facilitated immunotherapy show significant potential for treating inflammatory conditions.