Nanoarchitectonics of Copper Sulfide Nanoplating for Improvement of Computed Tomography Efficacy of Bismuth Oxide Constructs towards Drugless Theranostics

Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity, and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity, and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi2O3@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability towards dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency towards localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu2+ species for chemodynamic therapy (CDT) effects. To this end, the Bi3+ species in the core could be fully hydrated in the acidic tumor microenvironment (TME), resulting in GSH depletion and reducing CDT-induced reactive oxygen species (ROS) clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.