RNA-based liposomes for oral cancer: From biophysical characterization to biological evaluation.

Autor: Lopes-Nunes J; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal., Simões P; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal., Moreira D; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal., Leandro K; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal., Nobre RJ; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal; Viral Vectors for Gene Transfer Core Facility, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, 3030-789 16 Coimbra, Portugal., Pereira de Almeida L; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal; Viral Vectors for Gene Transfer Core Facility, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal., Campello MPC; Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal., Oliveira MC; Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal., Paulo A; Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal; Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, Portugal., Coutinho A; iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Dep. Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal., Melo AM; iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal., Tomaz C; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; Departamento de Química, Universidade da Beira Interior, Rua Marquês de Ávila e Bolama, 6201-001 Covilhã, Portugal., Cruz C; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; Departamento de Química, Universidade da Beira Interior, Rua Marquês de Ávila e Bolama, 6201-001 Covilhã, Portugal. Electronic address: carlacruz@fcsaude.ubi.pt.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Feb; Vol. 259 (Pt 2), pp. 129157. Date of Electronic Publication: 2024 Jan 08.
DOI: 10.1016/j.ijbiomac.2023.129157
Abstrakt: Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C 8 (acridine orange derivative) and dexamethasone to oral cancer cells were produced, characterized, and biologically evaluated. Firstly, the RNA structure and binding interaction with ligands (C 8 and dexamethasone) were evaluated by circular dichroism (CD), thermal difference spectroscopy (TDS), nuclear magnetic resonance (NMR) and fluorescence titrations. The biophysical assays evidenced the formation of an RNA hairpin and duplex structure. Moreover, steady-state and time-resolved fluorescence intensity and anisotropy experiments show that C 8 forms a complex with RNA and adopts an open conformation upon RNA binding. Then, RNA-coated liposomes were characterized by dynamic light scattering, and diameters near 160 nm were observed. Time-resolved anisotropy measurements of C 8 loaded in RNA-functionalized liposomes indicate the co-existence of free C 8 in solution (inside the liposome) and C 8 bound to RNA at the external liposome surface. The RNA-functionalized liposomes loaded with C 8 or dexamethasone mediated a significant reduction in the cell viability of malignant UPCI-SCC-154 cells while maintaining viable non-malignant NHDF cells. Additionally, the liposomes were able to internalize the cells, with higher uptake by the malignant cell line. Overall, the results obtained in this work can contribute to the development of new drug delivery systems based on RNA-coated liposomes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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