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Introduction. Osteosarcoma is the most common type of bone cancer diagnosed especially in children and young adults1. A combination of chemotherapy, radiotherapy and surgery is commonly used to treat this type of cancer2,3. In detail, chemotherapy is based on the use of molecules targeting the high cancer cell proliferation metabolism such as Platinum-based drugs that binds nuclear DNA upon overpassing the cell membrane, causing its damage and the arrest of the cancer cell cycle at G2/M transition phase, leading to apoptosis4-7. Despite Pt chemotherapeutics are the most potent used anticancer drugs, their side effects (high degradation before entering the cells, the off-target organs toxicity, and cell resistance) remain great drawbacks8-11.
Materials and methods. In this study, we synthetized Graphene oxide (GO)-based nanoplatforms as smart delivery systems of Platinum-based drug. In order to reduce GO cytotoxicity in health cells while promoting its cellular uptake in cancer cells, and to allow Pt loading on GO, 8-arm polyethylene glycol-amine (PEG) was used. The bioactivity of GO-PEG-Pt platforms were compared to Pt-free (15μM, 30μM, and 60μM) on three osteosarcoma cell lines (MG63, U2 and SAOS-2). The in vitro analysis of cellular uptake (ICP-OES), viability (MTT assay), morphology (actin and DAPI staining) and migration (scratch test) was performed.
Results. A preliminary study showed that GO-PEG was not toxic for cells at any concentration tested compared to cells only. A significant cell viability reduction was detected at 30 μM GO-PEG-Pt for all cell lines compared to Pt-free, reaching 70% cell mortality in MG63 (p value ≤ 0.0001) and SAOS-2 (p value ≤ 0.001). Morphological analyses showed a round-shape cell morphology and cell number reduction in the presence of GO-PEG-Pt respect to Pt-free in a dose dependent trend. Cellular uptake of GO-PEG-Pt was significantly higher after 24h for SAOS (p value ≤ 0.05) and MG63 (p value ≤ 0.0001) cell lines than Pt-free. The cell migration was lower in Go-PEG-Pt than Pt-free in MG63 and U2 with overall more than 60% migration inhibition over time at 30 µM concentration.
Conclusions. The results confirmed that GO-PEG-Pt platforms work as promising anticancer delivery systems. In fact, all the three osteosarcoma cell lines showed higher susceptibility to GO-PEG-Pt in terms of lower metabolic activity and lower migration rates due to the higher GO-PEG-Pt uptake compared to Pt-free.
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