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Thomas Flaig, MD

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Cisplatin-Induced Nephrotoxicity in Bladder Cancer: Gold Nanoparticles Under Study

By: Jenna Carter, PhD
Posted: Friday, October 20, 2023

Patients with advanced bladder cancer are often ineligible to receive standard cisplatin treatment because of the agent’s renal toxicity. An article recently published in Cancer Nanotechnology presented the use of a cisplatin-conjugated gold nanoparticle approach to circumvent issues with renal toxicity while preserving the therapeutic effects of cisplatin. Yoray Sharon, PhD, of the Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah Tikvah, Israel, and colleagues assessed the safety and efficacy of the nanoparticles in bladder tumor–bearing mice, using clinically relevant fractionated or nonfractionated dosing regimens. Their findings revealed that a nonfractionated high dose of cisplatin-conjugated gold nanoparticles blocked tumor growth, showed long-term intratumoral accumulation, and abolished the lethal effect of cisplatin. Additionally, as opposed to cisplatin alone, cisplatin-conjugated gold nanoparticles did not appear to cause fibrosis or necrosis in the kidney.

Cisplatin-conjugated 20-nm gold nanoparticles were synthesized and characterized before use in in vitro and in vivo experiments. MB49 mouse bladder cancer cell lines were cultured and used to assess cell survival after treatment with cisplatin alone or the conjugated type of the drug. Inductively coupled plasma optical emission spectroscopy was then used to determine tumor accumulation in mice following injections of the conjugated agent. This was followed by in vivo experiments in which the antitumor efficacy and safety of different dosing regimens were assessed using MB49 tumor-bearing mice.

Dose analyses revealed that nonfractionated high-dose (50 mg/kg) cisplatin-conjugated gold nanoparticles yielded long-term intratumoral accumulation (P < .05). Tumor growth analyses revealed inhibited tumor growth in mice treated with the conjugated drug regimen (P < .05). Additionally, treatment with fractionated lower doses (20 mg/kg) of the conjugated drug also led to increased intratumoral accumulation (P < .05) and prolonged mouse survival. Furthermore, safety analyses revealed that as opposed to free cisplatin, the cisplatin-conjugated gold nanoparticles did not cause kidney fibrosis or necrosis (P < .05).

Disclosure: The study authors reported no conflicts of interest.


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