Copper Sulfide-based Hollow Nanoarchitectonics for Augmented Photothermal, Chemodynamic, and Chemotherapeutic Modalities

Abstract

Cancer has become one of the dreadful ailments, accounting for millions of mortalities every year. Despite the advancements, it remains one of the appalling diseases, with numerous casualties due to delayed prognosis and poor survival rate. To this end, combinatorial strategies have garnered enormous interest in improved performance. This study aims to investigate the fabrication of transition metal-based hollow nanoarchitectures for synergistic augmented photothermal (PTT), chemodynamic (CDT), and chemotherapeutic (CT) modalities. Initially, copper sulfide nanoparticles with hollow cavities (hCuS) are synthesized using the facile sacrificial templating-based approach and subsequently loaded with the CT agent (Doxorubicin, DOX), referred to shortly as hCuS-DOX. These hCuS-DOX nanoarchitectures are systematically characterized using various techniques to successfully explore the physicochemical properties. The DOX molecules are encapsulated in hCuS containers through the electrostatic interactions due to their contrary charges and coordination interactions between copper in CuS and nitrogen in DOX molecules. These innovative nanoarchitectures showed pH-responsive release of DOX molecules from the hollow cavities, specifically in the tumor, which could be through the protonation of DOX and progressive degradation of hCuS. In addition, these architectures exhibited substantial PTT properties, on the one hand, by raising the temperature to over 60 °C. On the other hand, the released DOX molecules supported the CDT effect by generating enormous levels of deadly free radical species intracellularly, significantly reducing the viability of 4T1 cells. Finally, the apoptosis assay based on calcein AM/propidium iodide staining using various combinations validated the synergistic therapeutic modalities. In summary, these nanoarchitectures potentiated the synergistic therapeutic efficacy against breast carcinoma towards their ability in pharmaceutics.