POS-220 DEVELOPING RENAL CLEARABLE NANOPARTICLES FOR THE TREATMENT OF RENAL CELL CARCINOMA

Abstract

Nanoparticles (NPs) have been anticipated to revolutionise health care based on their potential to improve drug delivery. However, the design of effective cancer nano-therapeutics remains a challenge, and only a few nanoparticles have entered clinical trial. The majority of current NPs when administered intravenously are known to accumulate in lungs, liver, spleen & kidney and cause organ damage. Metastatic Renal Cell Carcinoma (RCC) is incurable, with median survival time of only 18 months, and currently there are no effective NP-based therapeutics. To effectively treat RCC and eliminate the side effects caused by NP organ accumulation, we have developed renal clearable NPs based on carbon material (Carbon Dots, CD). The aim of this project is to develop novel NPs with size less than 5.5nm as a vehicle to carry chemotherapeutic drugs such as Doxorubicin (DOX). The nanoparticles should possess renal clearable properties to target RCC and avoid non-specific distribution of drug causing adverse side effects. The study includes NP design and characterisation, drug conjugation, uptake of NPs and outcome measures. The properties of NPs were characterised, and the drug loading capacity was determined. The effect of drug and its conjugates were assessed initially in vitro. The pH difference between cancer cells and normal cells has been used as the triggering mechanism for DOX release. The cell viability of CD NPs, free DOX and CD-DOX conjugate were investigated in Renca and Hela cells by the MTT assay after 24 and 48 hr treatment. The development of an in vivo tumour model is in progress. We have successfully developed a novel type CD Nanoparticles by one-step synthesis. The Transmission Electron microscopy images revealed the CDs are spherical with an average diameter of 4nm. These CDs were shown to have low cytotoxicity with cell viability of higher than 90% at concentrations up to 200ug/ml; possess high quantum yield (58%) with bright blue fluoresce observed under UV light; very high drug loading capacity (93%). The maximum emission wavelength is at 440 nm upon excitation at 340 nm. The excitation-dependent photoluminescence properties allowed visual monitoring of the cells in blue, green and red fluorescence channels. The effective delivery and uptake of CDs into the cell’s cytoplasm was observed within 2 hrs by confocal microscopy. The cell viability assay demonstrated that CD-DOX significantly reduced the viability of the Renca cells by 2-fold compared to free DOX (24% vs 50% respectively, P value=0.0167). In Hela cells, the cell viability was furthermore reduced by 10-fold with CD-DOX compared to free DOX (5.5% vs 57.5% respectively, P value=0.0001). We have developed Carbon Dot nanoparticles with size <5.5nm with low cytotoxicity. The carbon dots have high drug loading capacity and show better inhibition of growth in cancer cell lines compared to unbound chemotherapeutics, suggesting that these nanoparticles have therapeutic potential in renal cell carcinoma.