A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs

Bogaert, Bram; Sauvage, Félix; Guagliardo, Roberta; Muntean, Cristina; Nguyen, Van Phuc; Pottie, Eline; Wels, Mike; Minnaert, An‐Katrien; Rycke, Riet De; Yang, Qingbiao; Peer, Dan; Sanders, Niek N.; Remaut, Katrien; Paulus, Yannis M.; Stove, Christophe; Raemdonck, Koen

doi:10.1016/j.jconrel.2022.08.009

Cited by 40 publications

(26 citation statements)

References 67 publications

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“…We can conclude that CQD internalization is likely cell-type dependent. Bogaert et al compared the uptake of CADs in easy-to-transfect cancer (HeLa) cells and hard-to-transfect primary cells (PBCECs,) and they observed that PBCECs had almost 50% less cell uptake, indicating that these cells are likely harder to penetrate . If the corneal epithelium is not the first target of the CQD-S 180 , the avoidance of cellular uptake presents an advantage for reaching the endothelium.…”

Section: Resultsmentioning

confidence: 99%

Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties

Hoon

Barras

Swebocki

et al. 2023

ACS Appl. Mater. Interfaces

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Reaching the corneal endothelium through the topical administration of therapeutic drugs remains a challenge in ophthalmology. Besides, endothelial cells are not able to regenerate, and diseases at this site can lead to corneal blindness. Targeting the corneal endothelium implies efficient penetration through the three corneal layers, which still remains difficult for small molecules. Carbon quantum dots (CQDs) have demonstrated great potential for ocular nanomedicine. This study focuses on the corneal penetration abilities of differently charged CQDs and their use as permeation enhancers for drugs. Excised whole bovine eyes were used as an ex vivo model to investigate corneal penetration of CQDs derived from glucosamine using β-alanine, ethylenediamine, or spermidine as a passivation agent. It was found that negatively charged CQDs have limited corneal penetration ability, while positively charged CQDs derived from glucosamine hydrochloride and spermidine (CQD-S) penetrate the entire corneal epithelium all the way down to the endothelium. CQD-S were shown to enhance the penetration of FITC-dextran 150 kDa, suggesting that they could be used as efficient penetration enhancers for therapeutic delivery to the corneal endothelium.

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Section: Resultsmentioning

confidence: 99%

Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties

Hoon

Barras

Swebocki

et al. 2023

ACS Appl. Mater. Interfaces

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“…[b] Measured in 20 mM HEPES buffer, pH 7.4. [c] Measured in 20 mM acetate buffer, pH 5.5 [40, 41] . [d] Measured by RiboGreen RNA assay, calculated as the fraction of encapsulated mRNA in LNP to total amount of mRNA used in the formulation.…”

Section: Resultsmentioning

confidence: 99%

“…Zeta-potential [c] @ pH 5.5 [mV] mRNA encapsulation efficiency [%] [d] Apparent pKa [e] PEG [c] Measured in 20 mM acetate buffer, pH 5.5. [40,41] [d] Measured by RiboGreen RNA assay, calculated as the fraction of encapsulated mRNA in LNP to total amount of mRNA used in the formulation.…”

Section: [Mv]mentioning

confidence: 99%

Visible Light Conjugation with Triazolinediones as a Route to Degradable Poly(ethylene glycol)–Lipids for mRNA Lipid Nanoparticle Formulation

et al. 2023

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Polyethylene glycol (PEG) is considered as the gold standard for colloidal stabilization of nanomedicines, yet PEG is non-degradable and lacks functionality on the backbone. Herein, we introduce concomitantly PEG backbone functionality and degradability via a one-step modification with 1,2,4triazoline-3,5-diones (TAD) under green light. The TAD-PEG conjugates are degradable in aqueous medium under physiological conditions, with the rate of hydrolysis depending on pH and temperature. Subsequently, a PEG-lipid is modified with TAD-derivatives and successfully used for messenger RNA (mRNA) lipid nanoparticle (LNP) delivery, thereby improving mRNA transfection efficiency on multiple cell cultures in vitro. In vivo, in mice, mRNA LNP formulation exhibited a similar tissue distribution as common LNPs, with a slight decrease in transfection efficiency. Our findings pave the road towards the design of degradable, backbonefunctionalized PEG for applications in nanomedicine and beyond.

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“…These drug molecules, due to their amphiphilic properties, accumulate in acidic lysosomes in their active form. The formed complex can be used to co-deliver mRNA within cationic amphiphilic drugs-assisted LNPs for various applications ( Bogaert et al, 2022 ). The approved LNP-based therapeutic formulations such as Patisiran (Alnylam), Elasomeran (Moderna) use similar ratios (50:10:38.5:1.5) of ILs, helper lipid (DSPC), cholesterol and polyethylene glycol lipids ( Suzuki and Ishihara, 2021 ; Ferraresso et al, 2022 ).…”

Section: Nanoparticles (Nps) Used For the Sirna Therapy Of Covid-19mentioning

confidence: 99%

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

Fopase

Panda

Rajendran

et al. 2023

Front. Bioeng. Biotechnol.

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Small interfering RNA (siRNA)-mediated mRNA degradation approach have imparted its eminence against several difficult-to-treat genetic disorders and other allied diseases. Viral outbreaks and resulting pandemics have repeatedly threatened public health and questioned human preparedness at the forefront of drug design and biomedical readiness. During the recent pandemic caused by the SARS-CoV-2, mRNA-based vaccination strategies have paved the way for a new era of RNA therapeutics. RNA Interference (RNAi) based approach using small interfering RNA may complement clinical management of the COVID-19. RNA Interference approach will primarily work by restricting the synthesis of the proteins required for viral replication, thereby hampering viral cellular entry and trafficking by targeting host as well as protein factors. Despite promising benefits, the stability of small interfering RNA in the physiological environment is of grave concern as well as site-directed targeted delivery and evasion of the immune system require immediate attention. In this regard, nanotechnology offers viable solutions for these challenges. The review highlights the potential of small interfering RNAs targeted toward specific regions of the viral genome and the features of nanoformulations necessary for the entrapment and delivery of small interfering RNAs. In silico design of small interfering RNA for different variants of SARS-CoV-2 has been discussed. Various nanoparticles as promising carriers of small interfering RNAs along with their salient properties, including surface functionalization, are summarized. This review will help tackle the real-world challenges encountered by the in vivo delivery of small interfering RNAs, ensuring a safe, stable, and readily available drug candidate for efficient management of SARS-CoV-2 in the future.

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A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs

Cited by 40 publications

References 67 publications

Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties

Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties

Visible Light Conjugation with Triazolinediones as a Route to Degradable Poly(ethylene glycol)–Lipids for mRNA Lipid Nanoparticle Formulation

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

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