Investigation of the antitumor activity and toxicity of cisplatin loaded pH-sensitive-pegylated liposomes in a triple negative breast cancer animal model

Abstract

Over the last decade, studies showed evidence of enhanced sensitivity of triple negative breast cancer (TNBC) to DNA-damaging agents, such as cisplatin (CIS), compared to other breast cancer subtypes. Despite its high efficacy, CIS has its use limited by dose-dependent side effects, mainly nephrotoxicity and neurotoxicity. In previous studies, it has been demonstrated by our research group that the encapsulation of CIS into pH-sensitive-PEGylated liposomes (pHPL-CIS) might allow to overcome some of its side effects. In the present work, we investigated the antitumor activity and toxicity of pHPL-CIS on Balb/c nude female mice bearing MDA-MB-231 tumor, a human TNBC cell line. Treatments with free-CIS or pHPL-CIS were both administered i.v. once a week for three weeks in cumulative doses of 12 and 30 mg/kg. Treatments in the higher dose allowed for similar tumor regression at the end of the experiment, however, the treatment with pHPL-CIS allowed for an earlier appearance of the antitumor effect. Additionally, animals receiving the higher dose of free-CIS presented weight loss, hepatic degeneration and 20% mortality rate, which was not observed for animals that received the high dose of pHPL-CIS. Thus, pHPL-CIS might be considered a promising candidate for the management of TNBC.