A novel intralymphatic nanocarrier delivery system for cisplatin therapy in breast cancer with improved tumor efficacy and lower systemic toxicity in vivo

BackgroundA lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity.MethodsHuman breast cancer cells (107 MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm3, intravenous cisplatin or subcutaneous hyaluronan-cisplatin (HA-cisplatin) nanoconjugate was given 1/week × 3 weeks at 3.3 mg/kg (platinum basis).ResultsNanoconjugates colocalized with the tumors after subcutaneous peritumoral injection and showed improved efficacy to intravenous cisplatin. After 1 month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared with subcutaneous HA-cisplatin nanoconjugates.ConclusionsThis nanocarrier delivery platform focuses on delivering drugs to the areas in which tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC.