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Lookup NU author(s): Eugenia Crisafulli, Annachiara Scalzone, Dr Piergiorgio GentileORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Royal Society of Chemistry. Osteosarcoma is one of the most common primary malignant bone tumours in children and adolescents, frequently arising from mesenchymal tissue in the distal femur. It is highly aggressive, often metastasising to the lungs. Current treatments, which include surgery combined with neoadjuvant chemotherapy and radiotherapy, are often unsatisfactory due to the inability of surgery to control metastasis and the side effects and drug resistance associated with chemotherapy. Thus, there is an urgent need for new treatment technologies. This study explored the use of nanoparticles for gene and drug delivery in osteosarcoma treatment. The nanoparticles were composed of biodegradable and biocompatible polymers, chitosan and PLGA, and were loaded with miRNA-34a, a short RNA molecule that functions as a tumour suppressor by inducing cell cycle arrest and apoptosis in osteosarcoma cells. Recognising that the co-delivery of multiple drugs can enhance treatment efficacy while reducing systemic toxicity and drug resistance, three additional classes of nanoparticles were developed by adding doxorubicin and resveratrol to the chitosan-PLGA-miRNA-34a core. A layer-by-layer technique was employed to create a bilayer nanocoating using pectin and chitosan as polyelectrolytes, for encapsulating the therapeutic payloads. The manufactured nanoparticles were tested on U2OS and Saos-2 cells to assess cell viability, metabolic activity, and morphology before and after treatment. Cells were treated in both two-dimensional cultures and three-dimensional osteosarcoma spheroids, creating a biomimetic cellular model. Increased apoptotic activity and disruption of cellular functions were primarily observed with nanoparticles co-delivering miRNA-34a and drugs, particularly those functionalised with the LbL nanocoating, as confirmed by PCR analysis.
Author(s): Crisafulli E, Scalzone A, Tonda-Turo C, Giron-Hernandez J, Gentile P
Publication type: Article
Publication status: Published
Journal: Journal of Materials Chemistry B
Year: 2024
Pages: Epub ahead of print
Online publication date: 29/10/2024
Acceptance date: 13/10/2024
Date deposited: 25/11/2024
ISSN (print): 2050-750X
ISSN (electronic): 2050-7518
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/d4tb01541j
DOI: 10.1039/d4tb01541j
Data Access Statement: The datasets supporting this article are available under request to the corresponding authors.
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