Tissue Engineering and Regenerative Medicine International Society (TERMIS) European Chapter Conference 2022

PLATINUM CONJUGATED TO NOVEL GRAPHENE OXIDE NANOPLATFORMS AS ANTICANCER THERAPY FOR GLIOBLASTOMA AND BREAST CANCER

Not scheduled

20m

ICE Krakow

poster PS49 Novel strategies to assess cellular response to biomaterials

Speaker

Arianna, Rossi (1. Institute of Science and Technology for Ceramics (Istec- Research National Council) 2. University of Messina)

Description

Introduction. Glioblastoma is a very aggressive type of cancer with a very poor life expectancy for patients and breast cancer often metastasizes into the liver, lungs, brain, and, in 70% of cases, to bones[1,2]. Chemotherapy is largely used to treat cancer and it is based on the use of molecules targeting the high cancer cell proliferation metabolism[3]. Platinum (Pt) and three of its isoforms (cisplatin, carboplatin, and oxaliplatin) are some of the most successful metal-based drugs to cure breast cancer and glioblastoma[4,5]. Despite Pt-based chemotherapeutics being effective, their side effects (high degradation before entering the cells, the off-target organs toxicity, and cell resistance) remain great drawbacks[6-9]. In this work, it was developed a Graphene Oxide (GO) nanoplatform functionalized with Pt as a promising smart delivery system that could increase the Pt cellular uptake reducing the Pt amount needed for cancer treatment and consequently the side effects.
Materials and methods. GO nanoplatforms were treated with 8-arm polyethylene glycol-amine (PEG) that permits to load Pt on the platform (GO-PEG-Pt) and an extensive in vitro screening was performed on two breast cancer cell lines with aggressive nature that lead to metastatic behavior (MDA-MB 231 and MDA-MB 468) and two glioblastoma cell lines (U87 and U118). The bioactivity of GO-PEG-Pt compared to Pt-free (15μM, 30μM, and 60μM) was analyzed looking at the effect on cellular uptake (ICP-OES), viability (MTT Assay), morphology (DAPI and actin staining), and migration up to 72 hours (Scratch Assay).
Results. The cell viability was significantly lower in MDA-MB 468 and U118 cells at 30μM for GO-PEG-Pt group compared to Pt-free (<75%), and even the cell morphology seemed to be compromised. These results were highly related to the cellular uptake of GO-PEG-Pt which is significantly higher compared to Pt-free after 24h. This data confirmed that our nanoplatform promotes drug delivery directly inside the cells. In addition, GO-PEG-Pt mostly affected the cell migration compared to Pt-free, in particular, MDA-MB 231 showed a migration reduction of 60%, and this could be a great advantage in reducing the metastasis process.
Conclusions. This study demonstrated that the combination of Pt onto PEG-functionalized nano-sized GO provided numerous advantages for tumor therapy such as minimizing toxicity, enhancing the cellular uptake, and consequently we could reduce the side effects because a lower amount of Pt is necessary.

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