pH-responsive nanoparticles based on POEOMA-b-PDPA block copolymers for RNA encapsulation, protection and cell delivery.

Autor: Baptista B; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal., Oliveira ASR; University of Coimbra, Centre for Mechanical Engineering, Materials and Processes, Department of Chemical Engineering, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal., Mendonça P; University of Coimbra, Centre for Mechanical Engineering, Materials and Processes, Department of Chemical Engineering, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal., Serra AC; University of Coimbra, Centre for Mechanical Engineering, Materials and Processes, Department of Chemical Engineering, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal., Coelho JFJ; University of Coimbra, Centre for Mechanical Engineering, Materials and Processes, Department of Chemical Engineering, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal., Sousa F; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: fani.sousa@fcsaude.ubi.pt.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2023 Feb; Vol. 145, pp. 213267. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1016/j.bioadv.2022.213267
Abstrakt: The use of gene-based products, such as DNA or RNA, is increasingly being explored for various innovative therapies. However, the success of these strategies is highly dependent on the effective delivery of these biomolecules to target cells. Therefore, the development of pH-responsive nanoparticles comprises the creation of intelligent delivery systems with high therapeutic efficiency. In this work, the pH-responsiveness of the poly(2-(diisopropylamino)ethyl methacrylate)) (PDPA) block was investigated for the encapsulation and delivery of small RNAs (sRNA) to cancer cells. The pH responsiveness was dependent on the protonation profile of the tertiary amines of PDPA, which directly affected the electrostatic interactions established with RNA. Thus, block copolymers based on poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA) and PDPA, POEOMA-b-PDPA, were synthesized by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP). The structure of the block copolymers was characterized by size exclusion chromatography and 1 H NMR spectroscopy. The copolymers allowed effective complexation of model sRNAs and a pre-miRNA with efficiencies of about 89 % and 91 %, respectively. The characterization by dynamic light scattering revealed that these systems had sizes between 76 and 1375 nm. It was also found that the morphology of the polyplexes depended on the pH, since the preparation at a pH lower than the pKa of the copolymers resulted in spherical but polydisperse particles, while higher pH values resulted in nanoparticles with more homogeneous size, but altered morphology. Moreover, due to pH-responsiveness, it was achieved the release of RNA at pH higher than the pKa of the copolymers, while maintaining its integrity. The polyplexes also showed a high potential to protect RNA from RNases. The transfection of a lung cancer model (A549) and fibroblast cell lines showed that these polyplexes did not cause cell toxicity. In addition, the polyplexes enabled the effective transfection of the A549 cell line with pre-miRNA-29b and miRNA-29b, resulting in a decrease of expression levels of the target DNMT3B gene by approximately 51 % and 47 %, respectively. Overall, the POEOMA-b-PDPA copolymers proved to be a promising strategy for developing responsive delivery systems, that can play a critical role in some diseases, such as cancer, where pH varies between the intra and extracellular environments.
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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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