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Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

Lookup NU author(s): Dr Liam Desmond, Simone Margini, Professor Anh Phan, Dr Piergiorgio GentileORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 Author(s).Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.


Publication metadata

Author(s): Desmond L, Margini S, Barchiesi E, Pontrelli G, Phan AN, Gentile P

Publication type: Article

Publication status: Published

Journal: APL Bioengineering

Year: 2024

Volume: 8

Issue: 1

Print publication date: 01/03/2024

Online publication date: 29/02/2024

Acceptance date: 06/02/2024

Date deposited: 18/03/2024

ISSN (electronic): 2473-2877

Publisher: American Institute of Physics Inc.

URL: https://doi.org/10.1063/5.0180831

DOI: 10.1063/5.0180831


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Funding

Funder referenceFunder name
EPSRC
EP/R51309X/1
IEC/R2/202094
International Exchanges 2020 Cost Share (Italy)
The Royal Society

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