Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe limitations with a lack of colloidal stability, reduced drug efficiency, and difficulties in storage conditions. Nanoarchaeosomes (NA) are a new generation of highly stable nanovesicles composed of the natural ether lipids extracted from archaea. In our study, we synthesized and characterized the NA, evaluated their colloidal stability, drug release potential, and anticancer efficacy. Transmission electron microscopy images have shown that the NA prepared from the hyperthermophilic archaeon Aeropyrum pernix K1 was in the size range of 61 ± 3 nm. The dynamic light scattering result has confirmed that the NA were stable at acidic pH (pH 4) and high temperature (70 °C). The NA exhibited excellent colloidal stability for 50 days with storage conditions at room temperature. The cell viability results have shown that the pure NA did not induce cytotoxicity in NIH 3T3 fibroblast cells and are biocompatible. Then NA were loaded with doxorubicin (NAD), and FTIR and UV-vis spectroscopy results have confirmed high drug loading efficiency of 97 ± 1% with sustained drug release for 48 h. The in vitro cytotoxicity studies in MCF-7 breast cancer cell lines showed that NAD induced cytotoxicity at less than 10 nM concentration. Fluorescence-activated cell sorting (FACS) results confirmed that NAD induced late apoptosis in nearly 92% of MCF-7 cells and necrosis in the remaining cells with cell cycle arrest at the G0/G1 phase. Our results confirmed that the NA could be a potential next-generation carrier with excellent stability, high drug loading efficiency, sustained drug release ability, and increased therapeutic efficacy, thus reducing the side effects of conventional drugs.
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