Effect of apoA-I PEGylation on the Biological Fate of Biomimetic High-Density Lipoproteins

Pedersbæk, Dennis; Krogager, Louise; Albertsen, Camilla Hald; Petersen, Lars; Hansen, Anders Elias; Jønsson, Katrine; Larsen, Jørgen Hannover; Kjær, Andreas; Andresen, Thomas Lars

doi:10.1021/acsomega.0c05468

Cited by 2 publications

(1 citation statement)

References 44 publications

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“…The results showed that PEGylation of the b‐HDL scaffold only had minimal effect on the biological fate of the lipids (Figure 3(a)). Both b‐HDL and PEG b‐HDL had similar biological fates (Pedersbæk et al, 2021). In contrast, Murphy et al demonstrated that reconstituted phospholipid/pegylated PEG‐ApoA‐I particles (PEG‐rHDL) markedly increased plasma half‐life and enhanced anti‐atherogenic properties in vivo compared with rHDL (Murphy et al, 2013).…”

Section: High‐density Lipoprotein‐mimicking Artificial Nanotherapeutic Developmentmentioning

confidence: 99%

Artificial high‐density lipoprotein‐mimicking nanotherapeutics for the treatment of cardiovascular diseases

Hong

2021

WIREs Nanomed Nanobiotechnol

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Despite the ability of current efficacious low‐density lipoprotein‐cholesterol–lowering therapies to reduce total cardiovascular disease (CVD) risks, CVD still poses major risks for morbidity and mortality to the general population. Because of the pleiotropic endothelial protective effects of high‐density lipoproteins (HDL), the direct infusion of reconstituted HDL (rHDL) products, including MDCO‐216, CER001, and CSL112, have been tested in clinical trials to determine whether direct infusion of rHDL can reduce coronary events in CVD patients. In addition to these rHDL products, in the past two decades, there has been an increased focused on designing artificial HDL‐mimicking nanotherapeutics to produce complementary therapeutic strategies for CVD patients beyond lowering of atherogenic lipoproteins. Although recent reviews have comprehensively discussed the developments of artificial HDL‐mimicking nanoparticles as therapeutics for CVD, there has been little assessment of “plain” or “drug‐free” HDL‐mimicking nanoparticles as therapeutics alone. In this review, we will summarize the clinical outcomes of rHDL products, examine recent advances in other types of artificial HDL‐mimicking nanotherapeutics, including polymeric nanoparticles, cyclodextrins, micelles, metal nanoparticles, and so on; and potential new approaches for future CVD interventions. Moreover, success stories, lessons, and interpretations of the utility and functionality of these HDL‐mimicking nanotherapeutics will be an integral part of this article. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

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Section: High‐density Lipoprotein‐mimicking Artificial Nanotherapeutic Developmentmentioning

confidence: 99%

Artificial high‐density lipoprotein‐mimicking nanotherapeutics for the treatment of cardiovascular diseases

Hong

2021

WIREs Nanomed Nanobiotechnol

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Mannose-functionalization of reconstituted high-density lipoprotein nanoparticles improves payload delivery and enhances M2-to-M1 phenotype reprogramming of RAW 264.7 macrophages polarized by B16-F10 melanoma cells

Dossou,

Mantsch,

Sabnis

et al. 2023

Front. Drug Deliv.

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The targeting and conversion of the immunosuppressive (M2) tumor-associated macrophages (TAMs) to an immunostimulatory (M1) phenotype can induce tumor regression in advanced melanoma. We have previously characterized and reported the ability of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) functionalized with DSPE-PEG-mannose (DPM) to deliver payload to macrophages. Herein, we investigate the modulation of macrophage phenotype and payload delivery mechanisms of the rHDL-DPM NPs in RAW 264.7 murine macrophages exposed to the conditioned medium (CM) from murine B16-F10 melanoma cells. The rHDL-DPM NPs loaded with the Stimulator of Interferon genes agonist, DMXAA, reduced protein levels of M2 markers. Through the mannose moiety, the rHDL-DPM-DMXAA NPs enhanced the production of interferon β and CXCL10 compared to the free DMXAA in the B16-F10 CM-educated RAW 264.7 macrophages. Compared to their non-mannosylated counterpart, the rHDL-DPM NPs delivered their payload more efficiently to the B16-F10 CM-educated RAW 264.7 macrophages. Mechanistically, both the scavenger receptor type B class 1 (SR-B1) and the mannose receptor (CD206) facilitated payload delivery to the macrophages via endocytic and non-endocytic mechanisms. Finally, the CM from rHDL-DPM-DMXAA NPs -treated macrophages enhanced paclitaxel (paclitaxel)-mediated cytotoxicity in B16-F10 cells. Together, these in vitro findings demonstrate the potential of the mannose-functionalized rHDL NPs in improving the targeting of M2-like TAMs and treatment outcomes when combined with immunotherapy or PTX in B16-F10 melanoma in vivo models.

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Effect of apoA-I PEGylation on the Biological Fate of Biomimetic High-Density Lipoproteins

Cited by 2 publications

References 44 publications

Artificial high‐density lipoprotein‐mimicking nanotherapeutics for the treatment of cardiovascular diseases

Artificial high‐density lipoprotein‐mimicking nanotherapeutics for the treatment of cardiovascular diseases

Mannose-functionalization of reconstituted high-density lipoprotein nanoparticles improves payload delivery and enhances M2-to-M1 phenotype reprogramming of RAW 264.7 macrophages polarized by B16-F10 melanoma cells

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