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- 01GJQM7ASW6Q9YJR12ZFZK4E97 classification A1.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 date "2022".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 language "eng".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 type journalArticle.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 hasPart 01GJQMZ1BZQ6FT9G7V6FNH99SA.pdf.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 hasPart 01GMD7WZH0B5XCRPXWM5K33ZRC.docx.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 subject "Biology and Life Sciences".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 subject "Medicine and Health Sciences".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 doi "10.1016/j.jconrel.2022.08.009".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 issn "0168-3659".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 issn "1873-4995".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 volume "350".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 abstract "Since the recent clinical approval of siRNA-based drugs and COVID-19 mRNA vaccines, the potential of RNA therapeutics for patient healthcare has become widely accepted. Lipid nanoparticles (LNPs) are currently the most advanced nanocarriers for RNA packaging and delivery. Nevertheless, the intracellular delivery efficiency of state-of-the-art LNPs remains relatively low and safety and immunogenicity concerns with synthetic lipid components persist, altogether rationalizing the exploration of alternative LNP compositions. In addition, there is an interest in exploiting LNP technology for simultaneous encapsulation of small molecule drugs and RNA in a single nanocarrier. Here, we describe how well-known tricyclic cationic amphiphilic drugs (CADs) can be repurposed as both structural and functional components of lipid-based NPs for mRNA formulation, further referred to as CADosomes. We demonstrate that selected CADs, such as tricyclic antidepressants and antihista-mines, self-assemble with the widely-used helper lipid DOPE to form cationic lipid vesicles for subsequent mRNA complexation and delivery, without the need for prior lipophilic derivatization. Selected CADosomes enabled efficient mRNA delivery in various in vitro cell models, including easy-to-transfect cancer cells (e.g. human cervical carcinoma HeLa cell line) as well as hard-to-transfect primary cells (e.g. primary bovine corneal epithelial cells), outperforming commercially available cationic liposomes and state-of-the-art LNPs. In addition, using the antidepressant nortriptyline as a model compound, we show that CADs can maintain their pharma-cological activity upon CADosome incorporation. Furthermore, in vivo proof-of-concept was obtained, demon-strating CADosome-mediated mRNA delivery in the corneal epithelial cells of rabbit eyes, which could pave the way for future applications in ophthalmology. Based on our results, the co-formulation of CADs, helper lipids and mRNA into lipid-based nanocarriers is proposed as a versatile and straightforward approach for the rational development of drug combination therapies.".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author 0711AED4-F0EF-11E1-A197-91C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author 7A896EDA-0091-11E8-84DC-A2E711A95AF2.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author B3A87470-036E-11E2-B63E-43C110BDE39D.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author E3D8F1FC-FF80-11E1-9705-E1D010BDE39D.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author EE916B9C-F3D2-11E6-9412-95BDAD28A064.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F4385BEC-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F4836E84-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F54C4980-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F5DB63F4-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F77C2766-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author F98B2FB6-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author FDB46C52-59C5-11E6-9EFD-DDF1B4D1D7B1.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author urn:uuid:1d493bd5-e431-41f1-b92c-1b1854bd2d9f.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author urn:uuid:6ef94920-901a-4d50-9120-932d78141acc.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author urn:uuid:7e3cc915-9500-46f2-bda5-89a3c3e41e11.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author urn:uuid:a13b3a7b-6700-4631-892d-27e472c80b0b.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 author urn:uuid:f1825b85-151f-404c-b79e-c78480468655.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 dateCreated "2022-11-25T14:49:18Z".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 dateModified "2024-11-27T23:56:28Z".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 name "A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs".
- 01GJQM7ASW6Q9YJR12ZFZK4E97 pagination urn:uuid:1a07b0bc-8b25-4127-9785-f3fa87d1365a.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 sameAs LU-01GJQM7ASW6Q9YJR12ZFZK4E97.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 sourceOrganization urn:uuid:55d9f660-b413-4039-a02e-b759945abb04.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 sourceOrganization urn:uuid:7ab906e7-b1f8-4db2-9d59-34439a19d66c.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 sourceOrganization urn:uuid:84260560-2e0a-474e-b714-cff6709c72ad.
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- 01GJQM7ASW6Q9YJR12ZFZK4E97 sourceOrganization urn:uuid:cd7be818-2161-4954-b777-387701a8df79.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 sourceOrganization urn:uuid:d684480a-a086-4c73-9914-4f028a8164b1.
- 01GJQM7ASW6Q9YJR12ZFZK4E97 type A1.