MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration

Genedy, Hussein H.; Humbert, Paul; Laoulaou, Bilel; Le Moal, Brian; Fusellier, Marion; Passirani, Catherine; Le Visage, Catherine; Guicheux, Jérôme; Lepeltier, Élise; Clouet, Johann

doi:10.1016/j.addr.2024.115214

Cited by 3 publications

(3 citation statements)

References 215 publications

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“…The choice of this range of DA was based both on the literature on CS-based noncoding RNA (ncRNA) delivery systems ,− and also on CS PEC. ,,,,,,,,, Small ncRNAs include microRNAs (miRNAs), small interfering RNAs (siRNAs), and piwi-interacting RNA(piRNAs) . In CS-based ncRNA nanocarriers research, based mainly on polyplexes rather than PECs, it is indeed always preferred to use CS of a lower DA (up to 30%) to obtain higher positive charge density capable of better condensation of genetic material. ,− , It is worth mentioning that the DA range used to realize these formulations lies within the transition domain of [25–50%], where CS, in solution, loses its hydrophilicity gradually as the DA % increases, balancing hydrophilic and hydrophobic interactions .…”

Section: Resultsmentioning

confidence: 99%

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems

Genedy,

Delair,

Alcouffe

et al. 2024

Biomacromolecules

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Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20−35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

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Section: Resultsmentioning

confidence: 99%

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems

Genedy,

Delair,

Alcouffe

et al. 2024

Biomacromolecules

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“…Recently, miRNA-based therapeutics have gradually translated from basic research to clinical application in the field of degenerative musculoskeletal diseases [ 10 – 15 ], which offers novel insights into precise miRNA-targeted treatments for IDD. However, the lack of an efficient NPC-specific delivery system hinders the application of miRNA-based therapeutics in vivo [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…With the rapid developments of nanomedicine, many biological delivery systems have been investigated for transferring miRNAs to treat IDD, including organic (polymeric or lipidic) nanoparticles [ 18 – 22 ], inorganic nanoparticles [ 23 , 24 ], nano-hydrogels [ 25 – 27 ], and extracellular vesicles (EVs) [ 28 – 30 ]. Different delivery systems possess different biological and release characteristics, and therefore hold promise for advancing the treatment of IDD [ 17 , 31 ]. For example, in vitro and in vivo studies have evaluated EVs characterization metrics, delivery methods, safety and efficacy profiles [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Jiang,

Qin,

Yang

et al. 2024

J Nanobiotechnol

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Background The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. Methods The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. Results We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. Conclusions NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD. Graphical Abstract

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Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering

Wang,

Zhang,

Cheng

et al. 2024

Pharmaceutics

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Intervertebral disc degeneration (IVDD) stands as the foremost contributor to low back pain (LBP), imposing a substantial weight on the world economy. Traditional treatment modalities encompass both conservative approaches and surgical interventions; however, the former falls short in halting IVDD progression, while the latter carries inherent risks. Hence, the quest for an efficacious method to reverse IVDD onset is paramount. Biomaterial delivery systems, exemplified by hydrogels, microspheres, and microneedles, renowned for their exceptional biocompatibility, biodegradability, biological efficacy, and mechanical attributes, have found widespread application in bone, cartilage, and various tissue engineering endeavors. Consequently, IVD tissue engineering has emerged as a burgeoning field of interest. This paper succinctly introduces the intervertebral disc (IVD) structure and the pathophysiology of IVDD, meticulously classifies biomaterials for IVD repair, and reviews recent advances in the field. Particularly, the strengths and weaknesses of biomaterials in IVD tissue engineering are emphasized, and potential avenues for future research are suggested.

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MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration

Cited by 3 publications

References 215 publications

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering

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