A ‘golden’ alternative for prevention of cisplatin nephrotoxicity in bladder cancer

Abstract

AbstractCisplatin (CP) is the first-line standard of care for bladder cancer. However, a significant percentage of advanced bladder cancer patients are ineligible to receive standard CP treatment, due to the drug’s toxicity, and in particular its nephrotoxicity. These patients currently face suboptimal therapeutic options with lower efficacy. To overcome this limitation, here we designed CP-conjugated gold nanoparticles (GNPs) with specific properties that prevent renal toxicity, and concurrently preserve the therapeutic efficacy of CP. Safety and efficacy of the particles were studied in bladder tumor-bearing mice, using clinically-relevant fractionated or non-fractionated dosing regimens. A non-fractionated high dose of CP-GNP showed long-term intratumoral accumulation, blocked tumor growth, and nullified the lethal effect of CP. Treatment with fractionated lower doses of CP-GNP was also superior to an equivalent treatment with free CP, demonstrating both anti-tumor efficacy and prolonged mouse survival. Moreover, as opposed to free drug, CP-conjugated GNPs did not cause fibrosis or necrosis in kidney. These results indicate that conjugating CP to GNPs can serve as an effective, combined anti-cancer and renoprotective approach, and thus has potential to widen the range of patients eligible for CP-based therapy.