F AZMI1,2, Q CAO1,2, G ZHENG1,2, P YE1, R WANG1, H LI1, T CHEN1,2, V LEE1,2, D HARRIS1,2,H DUONG2, Y WANG1,2
1Centre for Transplantation and Renal Research,The Westmead Institute for Medical Research, Westmead, Australia, 2Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Background: Chronic kidney disease (CKD) and Renal Cell Carcinoma (RCC) pose a great burden to global public health as current therapies are generally ineffective. Nanoparticles (NPs) have become a platform for targeted drug delivery in the treatment of various diseases & cancers. NPs with large size (>10 nm) or heavy metal components have significant concerns regarding long-term organ toxicity, limiting their clinical translation. Renal clearable NPs with size <6 nm can be excreted via kidneys and have great potential to decrease systemic toxicity by avoiding accumulation in healthy tissues/organs after systemic administration.
Aim: To develop novel NPs (carbon dots, CD) with size less than 6nm possessing renal clearable properties as a vehicle to carry drugs and inhibitors for specific targeting of RCC.
Methods: The effect of drug and its conjugates was assessed initially in vitro by MTT Assay after 24 and 48 hr treatment. The in vivo study is in progress.
Results: These CDs were shown to have very low cytotoxicity at concentrations up to 200ug/ml; possess high quantum yield (58%) with bright blue fluorescence observed under UV light; drug loading capacity for hydrophilic and hydrophobic compounds. The excitation-dependent photoluminescence properties allowed visual monitoring of the cells in blue, green and red fluorescence channels. The cell viability assay in Renca cells demonstrated that CDs carrying doxorubicin (CD-DOX) significantly reduced the viability of the Renca cells compared to free DOX (P value=0.0167). In Hela cells, the cell viability was also reduced with CD-DOX compared to free DOX (P value=0.0068).
Conclusions: The CDs and drug conjugate shows better inhibition of growth in cancer cell lines compared to the unbound chemotherapeutic, suggesting that these nanoparticles have therapeutic potential in RCC.
Farhana Azmi is currently a PhD candidate at the Centre for Transplantation and Renal Research. Her project involves working with novel nanoparticles in the treatment of Renal Cell Carcinoma. Her aim is to develop a renal clearable nanoparticle that can bind with both hydrophilic and hydrophobic drugs. Nanoparticles carrying drugs should result in better targeted delivery reducing side effects. Farhana has extensive interest in in the field of cancer research.
Her Master’s degree research involved Early Molecular Diagnosis of Prostate Cancer Using a Panel of Molecular Markers which was undertaken at Montreal General Hospital, McGill university, Canada.