PO-515 Novel water-solube [60]fullerene nanotherapeutic agent for pancreatic cancer treatment

• Published in: ESMO open 2018-07, Vol.3 (Suppl 2), p.A224-A224
• Main Authors: Serda, M, Ware, M, Newton, J, Sachdeva, S, Malarz, K, Musioł, R, Corr, S, Wilson, L, Curley, S
• Format: Article
• Language: English
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.530

IntroductionThe rapid development of nanotechnology is of great interest to researchers focused on translational medicine and novel targeted cancer treatment. This novel ‘nano’ approach has been used by medicinal chemist to design potential drugs which could easily broke almost any biological barriers. It has been published earlier, that engineered nanoparticles, including carbon nanomaterials, could enter tumours via their leaky vessels system and retain due to a weak drainage in the tumour microenvironment. Here we prestent the synthesis of water-soluble d-glucosamine derivatives used as drug delivery tools and selective FYN and LCK kinase inhibitor for pancreatic cancer treatment.Material and methodsHuman PDAC line PANC-1, ASCP-1 and PAN-O2 was obtained from American Type Culture Collection (ATCC, USA) or from National Cancer Institute. Nuclear magnetic resonance spectra were measured on a Bruker 400 MHz NMR Spectrometer with TMS as an internal standard. MS datasets were collected using Autoflex II MALDI-TOF mass spectrometer, and MS electrospray ionisation time-of-flight (ESI-microTOF) mass spectrometer, both instruments from Bruker Daltonics Inc (Fremont, CA). High-resolution spectra were performed using Shimadzu IT-ToF LC-MS System and flash chromatography was performed using Agilent 971-FP Flash Purification System.Results and discussionsTo date we have designed and synthesised three glucosamine-based, water-soluble [60]fullerene derivatives with high wate solubility up to 400 mg/ml. It was observed that all fullerenes form two aggregate fraction 20–30 nm and 400–500 nm. Initial dark cytotoxicity studies on pancreatic cancer cell line PANC1 have been carried out using flow cytometry and propidium iodide (PI) apoptosis staining. It has been shown that all 3 glycofullerenes are non-toxic even in high concentrations (up to 1 mg/ml, incubation 3 and 24 hours). Moreover, synthesised [60]fullerene derivative localises preferentially in the nucleus of PSC cells, with some localization in the cell cytoplasm.ConclusionOur results show predominant cellular nuclear internalisation of our novel hexakis glucosamine C60 derivative. In addition, synthesised nanotherapeutic is inherently non-toxic up to concentrations of 1 mg/ml, and displays strong photodynamic cytotoxic behaviour, when illuminated with both blue and green light. Moreover designed nanotherapeutic is showing selective inhibition to two kinases FYN A and LCK.MS thanks National Science Centre (Poland