Multifunctional Cu2-xTe Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453

Globally, basal-like breast cancers are documented to constitute 15-20% of all breast malignancies. They are characterized by aggressive cellular proliferation and short relapse times, culminating in poor patient prognosis. Breast cancers in general display a diverse range of biological, morphological and molecular subtypes defined by signature clinical characteristics. Basal-like breast cancers exhibit hyperactivity of DNA methylation as a result of DNA methyltransferase 3b (DNMT3b) overexpression, and simultaneous silencing of multiple methylation-sensitive genes. This typical feature resonates in the aggressive proliferation of basal-like breast cancer cells and translates in therapeutic resistance associated with them(1-7). Therefore, it is crucial that strategies addressing and overcoming these challenges be developed at the earliest. It is imperative that the conventional therapeutic strategies be augmented significantly and accordingly, to deal with such complexities. With remarkably diverse physicochemical properties, nanomaterials have tremendous prospects in medical treatment options. The integration of multiple functionalities such as specific cell targeting, fluorescent monitoring, drug/biomolecule accommodation, signature signal based sensing etc., in a single nano-entity offers a plethora of opportunities in strengthening the current anti-cancer therapeutic regimes(8-19). Inorganic nanoparticles as gold, metal sulfides etc., hold high-extinction coefficients in converting near-infrared (NIR) light to heat, and have been examined for photothermal therapy. Due to their tunable surface plasmon and NIR-thermal responsiveness, copper based chalcogenides seem promising in a wide range of biomedical applications and are ideally suited for theranostics(20-22). Being p-type semiconductors, copper based chalcogenides determine charge transport and provide a composition-dependent localized surface plasmon resonance (LSPR) in the near-infrared (NIR) region(23-26). In a recent work, Li et al. for the first time demonstrated the possibility of using as-made CuTe nanocrystals as a new NIR absorbing agent for in vitro-photothermal-killing of cancer cells(27). However, only a limited number of reports exist on Cu2Te, demonstrating its multifunctional theranostic capabilities. Herein, we developed size and shape tunable multifunctional Cu2-XTe nanocubes that presents a strong absorbance in the NIR region, ideal for photoacoustic (PAI) and X-ray contrast imaging. The nanocubes serve as highly effective chemo-photothermal-photodynamic cancer therapeutic combinatorial treatment agents that can overcome hypermethylated cancer cell resistance to chemotherapeutic drugs.