Developing Renal Clearable Nanoparticles for the Treatment of Renal Cell Carcinoma.

Abstract

Renal Cell Carcinoma (RCC) is the most common form of kidney cancer and has proven itself to be difficult to treat with conventional chemotherapy and radiotherapy. Nanoparticles (NPs), however, have been shown to significantly improve the efficacy of chemotherapy for RCC in recent years. A primary issue with using NPs is the safety concerns and potential side effects such as their permanent accumulation in major organs. To address this issue, the focus of my PhD study is the synthesis of novel non-toxic NPs that can be cleared by the kidneys or biocompatible/biodegradable NPs that can be used to deliver drugs/inhibitors to combat RCC. In this study, four type of renal clearable carbon dots and two types of biocompatible NPs have been developed. Among all these NPs, renal clearable NP called Sucrose Carbon Dots (Suc CDs) were created to carry hydrophilic drugs and Polymeric Micelles (P.M) were employed to carry hydrophobic drugs. Suc CDs ware developed with size <5 nm and showed strong fluorescence and high drug loading capacity for hydrophilic drugs, while P.M showed an excellent capability of loading hydrophobic drugs. In vitro study, both Suc CDs and P.M itself were shown to be non-toxic to normal tubule cells. Suc CDs conjugated to DOX showed better anticancer effects in Renca Cell line. Meanwhile, P.M loaded with insoluble drug of Everolimus (EVE) showed an enhanced inhibitory effect on cancer cells. In vivo carcinoma animal model, The Suc CDs loaded with DOX were more effective than DOX alone and had less toxicity to normal tubular cells. The accumulation of Suc CDs was observed in the tumour site for a longer time in tumour-bearing mice. The P.M conjugated to EVE significantly reduced the tumour size compared to drug alone. In conclusion, my study has demonstrated that Suc CDs+DOX and P.M+ EVE have superior anti-cancer activity and fewer side effects in both in vitro and in vivo studies. Furthermore, Suc CDs with DOX can be cleared by the kidneys with no accumulation in organ tissues, and the P.M are found to be biocompatible, with no toxicity. This indicates that these NPs have potential therapeutic applications for human RCC.