Melatonin-loaded lecithin and chitosan nanoparticles are cytotoxic to 4T1 breast cancer cells and safe in a BALB/c mouse model

Abstract

Melatonin is used as an adjuvant therapy in cancer treatment. However, its effectiveness is limited because of its low bioavailability. Polymeric nanoparticles (NPs) made of chitosan and lecithin have been developed to overcome this limitation and optimize localized drug delivery. These lecithin and chitosan-based NPs loaded with melatonin (NP-MEL) were evaluated for their cytotoxic potential in metastatic breast cancer cells and their safety profile in a murine model. Physicochemical characterization revealed efficient melatonin encapsulation (31 %), a positive zeta potential (48.6 mV), and controlled release at physiological pH. NP-MEL exhibited selective cytotoxicity in vitro, with a toxic concentration capable of killing 50 % of the cells (CC50) of 109.53 μg/mL for 4 T1 cancer cells and a significantly higher CC50 of 1460.59 μg/mL for normal VERO cells, resulting in a selectivity index of 13.33. In vivo experiments with BALB/c mice with tumor implantation treated with NP-MEL (2 mg/kg/day for 21 days) showed no significant changes in weight, clinical signs, or biochemical markers of liver and kidney function, except for changes in gamma-glutamyl transferase levels. Histopathological analyses confirmed the preservation of the liver and kidney architecture in the NP-MEL-treated group, in contrast to the moderate-to-severe kidney damage observed in animals treated with empty NPs. These findings highlight the low toxicity and therapeutic potential of NP-MEL as a controlled and targeted-release system for breast cancer treatment, indicating the need for further preclinical investigation.