Nanoarchaeosomes for synergistic photochemotherapy in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) poses significant therapeutic challenges due to the lack of targetable receptors and the systemic toxicity associated with conventional treatments such as surgery, radiotherapy, and chemotherapy. While phototherapy has emerged as a potential alternative, its clinical translation is hindered by the colloidal instability of photothermal agents and the need for combinatorial strategies. Here, we report the development of a near-infrared (NIR)-responsive theranostic nanoplatform based on archaeal lipid-derived nanoarchaeosomes (NA) co-encapsulating cisplatin (Cis) and PEGylated gold nanorods (AuNRs), forming a multifunctional NA-Cis-AuNRs nanoformulation. Archaeal lipids confer robust colloidal stability to this complex, enabling high drug-loading efficiency. Upon NIR irradiation, the AuNRs embedded within this complex generate localized hyperthermia, facilitating the rapid and controlled release of cisplatin. NA-Cis-AuNRs exhibit excellent biocompatibility in fibroblast cultures and zebrafish larvae, while effectively inducing apoptosis, oxidative stress, and associated DNA damage, and G2/M cell cycle arrest in TNBC cells. In vivo studies using the chick chorioallantoic membrane (CAM) assay confirm significant antiangiogenic activity, marked by downregulation of key angiogenic factors (VEGF, FGF2, and ANG1). Together, these results highlight a minimally invasive, NIR laser-triggered nanotherapeutic strategy with reduced systemic toxicity and establish a potential platform for TNBC treatment, warranting further preclinical validation in mammalian models.