(r)HDL in theranostics: how do we apply HDL's biology for precision medicine in atherosclerosis management?

Uribe, Kepa B.; Benito‐Vicente, Asier; Martín, César; Blanco‐Vaca, Francisco; Rotllan, Noemí

doi:10.1039/d0bm01838d

Cited by 5 publications

(6 citation statements)

References 174 publications

(173 reference statements)

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“…Finally, the efficiency of cholesterol efflux induced by sequential administration of antagomiR‐33a by DPPC:CE:LPC rHDL followed by DPPC rHDL was evaluated in macrophage‐derived foam cells loaded with TopFluor Cholesterol ( Figure A). [ 56 ] The efficiency of DPPC rHDL as cholesterol acceptor was compared with natural HDL (Figure 6B).…”

Section: Resultsmentioning

confidence: 99%

“…As mentioned above, a large number of studies have used rHDL as therapeutic agent addressing the central antiatherogenic and cardioprotective properties of HDL. [56,82] Inflammatory and atherogenic processes have been shown to be reduced by repeated infusion treatment with rHDL. [83] Therefore, sequential administration of antagomiR-33a-loaded rHDL followed by DPPC rHDL infusion could represent a good strategy to favor the reverse transport of cholesterol and contribute to the reduction of atheroma plaque.…”

Section: Discussionmentioning

confidence: 99%

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Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple‐Cell 2D Atherosclerosis Model

Jebari-Benslaiman

Uribe

Benito‐Vicente

et al. 2022

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Cardiovascular disease, the leading cause of mortality worldwide, is primarily caused by atherosclerosis, which is characterized by lipid and inflammatory cell accumulation in blood vessels and carotid intima thickening. Although disease management has improved significantly, new therapeutic strategies focused on accelerating atherosclerosis regression must be developed. Atherosclerosis models mimicking in vivo‐like conditions provide essential information for research and new advances toward clinical application. New nanotechnology‐based therapeutic opportunities have emerged with apoA‐I nanoparticles (recombinant/reconstituted high‐density lipoproteins, rHDL) as ideal carriers to deliver molecules and the discovery that microRNAs participate in atherosclerosis establishment and progression. Here, a therapeutic strategy to improve cholesterol efflux is developed based on a two‐step administration of rHDL consisting of a first dose of antagomiR‐33a‐loaded rHDLs to induce adenosine triphosphate‐binding cassette transporters A1 overexpression, followed by a second dose of 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine rHDLs, which efficiently remove cholesterol from foam cells. A triple‐cell 2D‐atheroma plaque model reflecting the cellular complexity of atherosclerosis is used to improve efficiency of the nanoparticles in promoting cholesterol efflux. The results show that sequential administration of rHDL potentiates cholesterol efflux indicating that this approach may be used in vivo to more efficiently target atherosclerotic lesions and improve prognosis of the disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple‐Cell 2D Atherosclerosis Model

Jebari-Benslaiman

Uribe

Benito‐Vicente

et al. 2022

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“…High‐density lipoprotein (HDL) is a nanoparticle with a diameter of ≈10 nm and antiatherogenic properties; [ 6 ] its nascent form has been reconstituted with recombinant apolipoprotein A‐I and phosphatidylcholine. [ 7 ] We previously reported that a library of the engineered nascent forms with different CPPs, phospholipids, and sizes were screened for the efficiency of posterior drug delivery via eye‐drop instillation, and the form with the best efficiency provided therapeutic efficacy in a mouse model of neovascular AMD. [ 8 ] Importantly, therapeutic efficacy was observed for both drug cargo and HDL variant.…”

Section: Introductionmentioning

confidence: 99%

High‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degeneration

Fukuda,

Mahmuda,

Kasirawat

et al. 2023

Advanced Therapeutics

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Eye‐drop treatments of age‐related macular degeneration (AMD) are desirable; however, no clinically approved eye drop has been reported to date. This study aimed to evaluate the therapeutic activity of eye‐drop instillation of a high‐density lipoprotein (HDL) variant bearing a cell‐penetrating peptide and neovasculature‐targeted peptide (AsnGlyArg [NGR] peptide) in a mouse model at a dose of 0.6–0.85 μg protein/eye drop. The results revealed that the activity of the abovementioned variant was >10‐fold higher than that of our previous variant lacking an NGR peptide. In addition, the anti‐inflammatory activity, cholesterol‐efflux capacity, and antiangiogenic activity of reconstituted HDL were significantly augmented by the attachment of these two peptides. The mechanism underlying this dramatic improvement is likely the expression of CD13, an NGR peptide receptor, on the cornea and conjunctiva in mice. CD13 mRNA/protein expression was also detected in cultured human corneal and conjunctival cells. These results demonstrate that NGR peptide is an unprecedented class of an absorption enhancer on the eye surface. Thus, HDL engineering is a potential strategy for developing eye drops to treat neovascular AMD by enhancing the ocular surface absorption and HDL functionalities.This article is protected by copyright. All rights reserved

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“…Discoidal high-density lipoprotein (HDL) is characterized by the association of amphiphilic apoproteins (apoA-I) to phospholipid membrane discs with a size of approximately 10 nm, which can be easily reconstituted in vitro . − Recent research has shown that synthetic HDL functions as a drug nanocarrier because of its small size, amphiphilic nature, and biocompatibility. − In previous research, we produced an HDL variant containing an amphiphilic cationic peptide penetratin and 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC), designated as engineered lipoprotein 1 (eLP1), and a drug–eLP1 complex eye drop was instilled in a mouse model of age-related macular degeneration to demonstrate significant therapeutic efficacy . Importantly, the efficacy of the eLP1 formulation was greater than that of the liposomal formulation.…”

mentioning

confidence: 99%

Comprehensive Analysis of Drug Loading into Engineered Lipoprotein Nanoparticles toward Their Eye Drop Application

Fukuda,

Shima,

Shibukawa

et al. 2023

ACS Appl. Bio Mater.

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The drug loading capacity of an engineered lipoprotein (eLP1) and the colloidal stability of drug-loaded eLP1s were assessed with 12 drugs with different charges/hydrophobicities. The capacity was largely correlated with their log P values, and the binding to the protein moiety was suggested for two drugs. The size of drug-loaded eLP1 formulations after freeze-drying followed by resolubilization hardly changed. The eLP1 formulation of travoprost, a clinically used drug in eye drop formulations, maintained its small size (19 nm) for 1 h at 37 °C in an artificial tear solution, whereas the liposome counterpart of 112 nm in diameter aggregated.

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(r)HDL in theranostics: how do we apply HDL's biology for precision medicine in atherosclerosis management?

Abstract: (r)HDL therapeutics has progressed a long way but has yet to produce fruitful results. Based on what has been learned and on the most innovative perspectives, a new generation of “smart” rHDL is emerging as an alternative for the management of CVD.

Cited by 5 publications

References 174 publications

Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple‐Cell 2D Atherosclerosis Model

Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple‐Cell 2D Atherosclerosis Model

High‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degeneration

Comprehensive Analysis of Drug Loading into Engineered Lipoprotein Nanoparticles toward Their Eye Drop Application

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