Table 1.
Novel rHDL NPs developed for atherosclerosis treatment.
| Year | Group | HDL | Animal model | Key Findings | Ref. |
|---|---|---|---|---|---|
| 2017 | Liu | HA-PLGA-ST-rHDL | NZW rabbits | 1) Avoided liver clearance and increased the accumulation of NPs at the leaky endothelium compared to HA unmodified NPs; 2) showed better cholesterol efflux and accumulation in atherosclerotic aortic root in vivo. | [88] |
| 2017 | Liu | DXS-AT-rHDL | N/A | 1) Demonstrated better macrophage targeting than PLGA-rHDL NPs without modification; 2) exhibited better efficacy in preventing foam cell formation and inflammation. | [89] |
| 2017 | Mulder | ST-rHDL | ApoE−/− mice | 1) Demonstrated similar accumulation within macrophages in plaque as ST-polymer micelles, which was better than that of ST-liposomes; 2) showed less accumulation in monocytes and efficacy in reducing macrophage burden than ST-polymer micelles. | [90] |
| 2017 | Liu | rHDL-anti-miR-155 | N/A | 1) Escaped from endolysosomes via clathrin-mediated endocytosis; 2) showed high transfection efficiency; 3) induced cholesterol efflux and antioxidation. | [91] |
| 2018 | Chen | LT-GM1-rHDL | ApoE−/− mice | 1) Showed an extended circulation time, better accumulation in plaque, and stronger anti-atherogenic ability in vivo compared to unmodified LT-rHDL NPs; 2) demonstrated better inhibition of foam cell formation in vitro. | [92] |
| 2018 | Liu | HA-PLGA-rHDL NPs loaded with LOX-1 siRNA and AT | ApoE−/− mice | Targeted ECs and macrophages; efficacy for atherosclerosis increased as HA molecular weight increased; 3) LOX-1 siRNA and AT demonstrated synergistic therapeutic efficacy. | [93] |
| 2019 | Liu | ATP-rHDL NPs, loaded with SR-A siRNA and oxygen-evolving catalase, PtdSer, and PT | ApoE−/− mice | 1) Demonstrated the effectiveness of apoA-I and PtdSer for targeting SR-BI and CD36 receptors; 2) showed excellent targeting ability; 3) induced 65.8% plaque reduction in vivo. | [94] |
| 2018 | Lutgens | TRAF6-rHDL NPs: rHDL NPs loaded with inhibitor (687702), targeting the interaction between CD40 and TRAF6 while leaving CD40 mediated immunity intact | ApoE−/− mice and non-human primates | 1) Reduced monocyte recruitment and suppressed the initiation of atherosclerosis in mice by decreasing CD40 and integrin expression in monocytes; 2) stabilized plaque and suppressed the progression of plaque in mice; 3) lowered macrophage and T cell contents in mice aorta; 4) downregulated genes controlling monocyte migration and upregulated genes affecting lymphocyte homing in mice; 5) exhibited non-toxicity to mice and non-human primates. | [84, 95, 96] |
| 2020 | Liu | β-cyclodextrin and ST-loaded discoidal rHDL | shuttle/sink model | 1) Demonstrated better ability to remove cholesterol than ST-rHDL without β-cyclodextrin; 2) the concentration of β-cyclodextrin has a positive effect on the rHDL cholesterol removal capability for foam cells. | [97] |
Notes and Abbreviations: rHDL: reconstituted high-density lipoprotein; NP: nanoparticle; HA: hyaluronic acid; PLGA: poly (lactic-co-glycolic acid); ST: statin; NZW: New Zealand white; DXS: dextran sulfate; AT: atorvastatin; ApoE−/−: Apolipoprotein E-deficient; anti-miR-155: against microRNA-155; LT: lovastatin; GM1: monosialoganglioside; LOX-1: lectin-like oxidized low-density lipoprotein receptor-1; siRNA: small interfering ribonucleic acid; EC: endothelial cells; MCP-1: monocyte chemoattractant protein-1; ATP: adenosine triphosphate; SR-A: scavenger receptor class A; PtdSer: phosphatidylserine; PT: pitavastatin; apoA-I: Apolipoprotein A1; SR-BI: scavenger receptor class B type 1; TRAF6: tumor necrosis factor receptor-associated factor 6; CD40 and CD36: cluster of differentiation 40,and 36.