Multimodal layer-by-layer nanoparticles: a breakthrough in gene and drug delivery for osteosarcoma

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-12, Vol.12 (48), p.1254-12552
• Main Authors: Crisafulli, Eugenia, Scalzone, Annachiara, Tonda-Turo, Chiara, Girón-Hernández, Joel, Gentile, Piergiorgio
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biocompatibility; Biodegradation; Biomimetics; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Bone surgery; Bone tumors; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Chemotherapy; Chitosan; Chitosan - chemistry; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug resistance; Drug Screening Assays, Antitumor; Femur; Gene Transfer Techniques; Humans; Layer-by-Layer Nanoparticles; Metastases; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Nanoparticles; Nanoparticles - chemistry; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - pathology; Osteosarcoma cells; Particle Size; Payloads; Pectin; Polyelectrolytes; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polylactide-co-glycolide; Polymers; Radiation therapy; Resveratrol; Resveratrol - chemistry; Resveratrol - pharmacology; Side effects; Spheroids; Surgery; Toxicity; Tumor suppressor genes; Tumors
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb01541j

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. This study explored biodegradable nanoparticles for treating osteosarcoma. Co-delivery of miRNA-34a, doxorubicin, and resveratrol by LbL nanocoating enhanced apoptosis and cell disruption with promise to improve efficacy and reduce drug resistance.