Study of the biodistribution of the cisplatin-based Pt(IV) dual prodrug Riboplatin by fluorescence imaging

Abstract

BACKGROUND: There is an urgent need to develop new platinum-based anti-tumor agents that are both more effective and less toxic. One strategy for developing these drugs is the synthesis of Pt(IV) prodrugs, which are precursor complexes of cisplatin and its analogues capable of releasing active Pt(II) drugs directly into the intracellular environment of malignant neoplasms. To identify the optimal method of in vivo administration of a new platinum-based drug, it is essential to assess its acute toxicity and biodistribution in vital organs. AIM: Study of tolerability, acute toxicity, biodistribution and ability to accumulate in breast tumors of the drug Riboplatin, as well as its liposomal form. MATERIALS AND METHODS: The study was conducted at the Moscow Pedagogical State University. The study was carried out on BALB/C mice, female, weight 22-25 g, age 5-6 weeks, healthy or grafted mammary adenocarcinoma EMT-6, as well as in immunodeficient BALB/C nude mice, female, weight 20-22 g, age 4-5 weeks with grafted human mammary adenocarcinoma SK-BR-3 by fluorescence imaging and inductively coupled plasma mass spectrometry. RESULTS: Riboplatin was shown to be highly tolerable after a single intravenous dose up to a dose of 48 mg/kg. Fluorescence imaging showed the ability of Riboplatin and its liposomal formulation to effectively accumulate in EMT-6 tumors 70 minutes after intravenous administration. Riboplatin shows the ability to deliver platinum to the SK-BR-3 tumor and that the drug reaches the tumor as a prodrug. ICP-MS analysis of liposomal formulation results suggests accumulation and metabolism of liposomes in the spleen of mice. CONCLUSION: Riboplatin is a Pt(IV) prodrug with high tolerability, reduced toxicity compared to cisplatin, and is able to accumulate effectively in malignant breast tumors. The possibility of fluorescence imaging of Riboplatin drug biodistribution in vivo in tumor lines EMT-6 and SK-BR-3 has been demonstrated. The high level of Riboplatin accumulation in EMT-6 tumors suggests riboflavin-specific uptake.