Quercetin-loaded nanoarchaeosomes for breast cancer therapy: a ROS mediated cell death mechanism

Abstract

Breast cancer is the deadliest disease among women due to the lack of novel targeted therapies. Flavonoid compounds like quercetin exhibit excellent anticancer activity. However, quercetin's high hydrophobicity, poor solubility, and low bioavailability limit its therapeutic efficacy. Several systems, like polymeric, metallic, and liposomal nanomaterials, have been designed to enhance quercetin's therapeutic efficacy. However, these nanocarrier systems lack colloidal stability and biocompatibility and have poor drug-loading efficiency. Herein, we have synthesized thermostable quercetin-loaded nanoarchaeosomes (NAQ) for effective breast cancer treatment. The synthesized NAQ have a size of 53.5 ± 1 nm. The drug loading efficiency was 99 ± 0.2%, and sustained drug release kinetics was observed. Furthermore, to determine the in vitro anticancer potential of NAQ, we have used the breast cancer cell line MCF-7 as a model. The NAQ induced significant cell death in breast cancer cells by generating reactive oxygen species (ROS), resulting in an IC₅₀ value of 2.5 μM. The observed IC₅₀ value was thirty-five-fold less than the IC₅₀ value of quercetin alone treated MCF-7 cells. The flow cytometry and cell cycle analyses confirmed that NAQ induced necroptosis with cell cycle arrest at the G0/G1 phase. The NAs and NAQ exhibit excellent biocompatibility in normal fibroblast cells NIH 3T3. Our findings suggest that NAQ have good biocompatibility, stability, and drug loading and release kinetics and can act as an effective alternative anticancer nanotherapeutic agent against breast cancer by minimizing the side effects.