High-Density Lipoprotein Nanobiologics for Precision Medicine

Abstract

Nature is an inspirational source for biomedical engineering developments. Particularly, numerous nanotechnological approaches have been derived from biological concepts. For example, among many different biological nanosized materials, viruses have been extensively studied and utilized, while exosome research has gained much traction in the 21st century. In our body, fat is transported by lipoproteins, intriguing supramolecular nanostructures that have important roles in cell function, lipid metabolism, and disease. Lipoproteins' main constituents are phospholipids and apolipoproteins, forming a corona that encloses a hydrophobic core of triglycerides and cholesterol esters. Within the lipoprotein family, high-density lipoprotein (HDL), primarily composed of apolipoprotein A1 (apoA-I) and phospholipids, measuring a mere 10 nm, is the smallest and densest particle. Its endogenous character makes HDL particularly suitable as a nanocarrier platform to target a range of inflammatory diseases. For a decade and a half, our laboratories have focused on HDL's exploitation, repurposing, and reengineering for diagnostic and therapeutic applications, generating versatile hybrid nanomaterials, referred to as nanobiologics, that are inherently biocompatible and biodegradable, efficiently cross different biological barriers, and intrinsically interact with immune cells. The latter is facilitated by HDL's intrinsic ability to interact with the ATP-binding cassette receptor A1 (ABCA1) and ABCG1, as well as scavenger receptor type B1 (SR-BI). In this Account, we will provide an up-to-date overview on the available methods for extraction, isolation, and purification of apoA-I from native HDL, as well as its recombinant production. ApoA-I's subsequent use for the reconstitution of HDL (rHDL) and other HDL-derived nanobiologics, including innovative microfluidic-based production methods, and their characterization will be discussed. The integration of different hydrophobic and amphiphilic imaging labels, including chelated radioisotopes and paramagnetic or fluorescent lipids, renders HDL nanobiologics suitable for diagnostic purposes. Nanoengineering also allows HDL reconstitution with core payloads, such as diagnostically active nanocrystals, as well as hydrophobic drugs or controlled release polymers for therapeutic purposes. The platform technology's specificity for inflammatory myeloid cells and methods to modulate specificity will be highlighted. This Account will build toward examples of in vivo studies in cardiovascular disease and cancer models, including diagnostic studies by magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). A translational success story about the escalation of zirconium-89 radiolabeled HDL (Zr-HDL) PET imaging from atherosclerotic mice to rabbits and pigs and all the way to cardiovascular disease patients is highlighted. Finally, recent advances in nanobiologic-facilitated immunotherapy of inflammation are spotlighted. Lessons, success stories, and perspec...

Nanotherapy that prevents trained immunity and promotes tolerance

“…1 The nanomimmunotherapy consisted of high-density lipoprotein (HDL) nanobiologics, which they previously reported to specifically target myeloid cells in vivo. 2 In the current study, the authors demonstrate that HDL-nanobiologics target myeloid cells in the heart allograft and myeloid cell precursors in the bone marrow of transplant recipient mice. The latter characteristic of HDLnanobiologics is critical for the long-term efficacy.…”

“…To enhance therapeutic efficacy, the authors complemented the mTORi-HDL treatment with a CD40-TRAF6 specific nanobiologic (TRAF6i-HDL) that inhibits co-stimulation. 2 This synergistic nanoimunnotherapy resulted in indefinite allograft survival, without signs of toxicity.…”

High density lipoprotein mimicking nanoparticles for atherosclerosis

“…Thus, HDL mimicking NPs can exist as either discoidal or spherical in shape. With that in mind, the production of HDL mimicking NPs is mainly accomplished via two general approaches: reconstitution and microfluidic homogenization [21]. Reconstitution is the traditional method of fabricating HDL mimicking NPs where HDL is reconstituted from apoA-I and phospholipids.…”

Topical administration of nanocarrier miRNA‐210 antisense ameliorates imiquimod‐induced psoriasis‐like dermatitis in mice

“…16,17 The NG-control mice were treated with the same dose of vehicle gel. 16,17 The NG-control mice were treated with the same dose of vehicle gel.…”

“…For NG-anti-miR-210 treatment, the IMQ-treated mice were further administrated 110 mg NG-anti-miR-210 at 150 or 300 nmol/L twice a day according to related articles. 16,17 The NG-control mice were treated with the same dose of vehicle gel. All mice in each group were killed at the 7th day.…”