Tumor microenvironment responsive CuV/DTPA@Catalase/5-fluorouracil nanodrug for reactive oxygen species modulation and breast cancer imaging.

Abstract

Breast cancer remains a leading cause of cancer-related mortality among women, necessitating the development of targeted and effective therapeutics. This study presents a multifunctional nanodrug system, CuV/DTPA@Catalase/99mTc-5FU, engineered for enhanced anticancer efficacy and imaging. Copper-doped vanadium nanoparticles were functionalized with DTPA to form a complex, followed by interaction with catalase-modified 5-fluorouracil (5-FU). The nanodrug was radiolabeled with technetium-99 m (99mTc) for nuclear imaging. Characterization via UV-Vis, FTIR, XRD, SEM, and HPLC confirmed successful synthesis and drug loading, with particle sizes ranging from 20 to 100 nm. The nanodrug exhibited pH- and temperature-responsive drug release, achieving ~80% cumulative release at pH 6.5 and 40 °C over 24 h. In vitro assays on MCF-7 breast cancer cells demonstrated greater than 93.87% ± 4.44 cell death. While cell viability was 6.13% ± 3.55, significantly outperforming free 5-FU. Mechanistically, catalase integration facilitated the scavenging of reactive oxygen species (ROS). In addition, catalase inhibited NF-κB activation and reversed multidrug resistance (MDR). Immunoblotting confirmed reduced p-p65 and elevated IκBα levels in treated cells, indicating suppressed NF-κB signaling. The radio-labeling of the nanodrug showed a bound drug percentage of 97.56%. In vivo SPECT-CT imaging revealed high radiochemical stability and selective biodistribution, with greater than 34% accumulation in breast tissue. The CuV/DTPA@Catalase/99mTc-5-FU platform offers synchronized chemotherapy, redox modulation, and diagnostic imaging. These features highlight its potential as a tumor-targeted, ROS-responsive nanotherapeutic that can overcome limitations of conventional chemotherapy by regulating the NF-κB pathway and enabling precise drug delivery.