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Systemic drug co-delivery system with miR-34a and doxorubicin assembled by layer-by-layer (LbL) for osteosarcoma treatment

Rebecca Silvestris

Systemic drug co-delivery system with miR-34a and doxorubicin assembled by layer-by-layer (LbL) for osteosarcoma treatment.

Rel. Irene Carmagnola, Piergiorgio Gentile. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2023

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Osteosarcoma is a primary malignant bone tumor with elevated mortality rates in youngsters and adolescents. Current therapeutic approaches entail preliminary chemotherapy followed by surgical removal and supplementary chemotherapy. Roughly 30% of patients experience recurrence, underscoring the limitations, as surgery alone cannot effectively manage metastasis. Nanoparticle-mediated targeted drug delivery systems present a promising therapeutic avenue for osteosarcoma, as they overcome the constraints of conventional chemotherapy by augmenting retention, permeability, and active targeting. Objectives Devise and construct systemic drug co-delivery systems by utilizing nanoscale modification of miR-34a and doxorubicin via layer-by-layer (LbL) assembly for precise osteosarcoma treatment. Approaches PLGA-CS polyplexes were produced using optimized nano-complexation and LbL assembly techniques. LbL-NPs were examined on two-dimensional SaoS-2 and U2OS cell models to gauge metabolic activity and cellular demise via PrestoBlue and Live/dead assessments. Encapsulation efficiency and drug release kinetics were appraised using the QuantiFluor® RNA System and UV-VIS Spectroscopy. Findings Manufactured PLGA-CS polyplexes exhibited impressive mean encapsulation efficiencies for miR-34a and doxorubicin, 99.97% and 69.74%, respectively. Only the fabricated LbL-NPs P4 and PC4 displayed substantial, sustained release of miR-34a over a ten-day period (P-value 0.002 and 0.011). All LbL-NPs, at concentrations of 500 and 1000µg/ml, markedly diminished the metabolic activity of U2OS cells after five days of incubation (P-value <0.001). LbL-NPs P5 and PC5 induced apoptotic activity and cell demise in U2OS cells. Conclusion The engineered PLGA-CS polyplexes and LbL-NPs serve as effective nanocarrier systems, inducing cytotoxicity by delivering tumor-suppressing miR-34a and doxorubicin into in vitro osteosarcoma cell models. The incorporation of hyaluronic acid and additional nanocoating further enhances the cytotoxicity of LbL-NPs against U2OS cells through active targeting.

Relators: Irene Carmagnola, Piergiorgio Gentile
Academic year: 2023/24
Publication type: Electronic
Number of Pages: 95
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: The University of Newcastle upon Tyne
URI: http://webthesis.biblio.polito.it/id/eprint/28913
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