Computational modeling and experimental synthesis of BSA-coated bimetallic theranostic MnO₂-Au@curcumin nanoplatform for synergistic radiochemotherapy of breast cancer.

This study details the design, synthesis, and validation of the novel MnO₂-Au-BSA@CUR construct, utilizing a tightly integrated computational (Docking, DFT, MD) and experimental approach to understand its structure and function, and demonstrating significant in vitro synergistic radiosensitization as a key outcome for potential breast cancer therapy. The nanoparticles, comprising manganese dioxide (MnO) for oxygen generation, gold (Au) for radiosensitization, bovine serum albumin (BSA) for biocompatibility, and curcumin (CUR) for dual chemotherapeutic and radioprotective effects, were synthesized and characterized using techniques such as UV-Vis spectroscopy, XRD, FTIR, and TEM, confirming their uniform morphology and successful conjugation. As shown in the TEM image, the average size of MnO-Au-BSA@CUR nanoparticles is about 39.25 nm, with a spherical shape. DLS results show the hydrodynamic size of MnO-Au-BSA@CUR nanoparticles with a Z-average of 190 nm with polydispersity index (PdI) of nanoparticles to be 0.391 and zeta potential of nanoparticles is -24.7 mV. In vitro studies on 4T1 breast carcinoma cells demonstrated dose-dependent cytotoxicity and enhanced radiosensitization under 4 Gy X-ray irradiation, attributed to Au's increased X-ray absorption and CUR's synergistic action. The pH-dependent release of CUR, significantly enhanced under acidic conditions, represents a key design feature for promoting tumor-specific delivery and minimizing systemic exposure. Computational analyses, including molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations, elucidated the nanoplatform's stability and interactions, revealing strong binding energies (-89.23 kcal/mol for CUR with α-MnO₂-Au (111)) and a narrow HOMO-LUMO gap (2.05 eV) that supports efficient charge transfer for radiosensitization. This study establishes the MnO-Au-BSA@CUR nanoplatform as a promising theranostic agent, integrating experimental and computational insights to advance multifunctional nanomedicine for cancer therapy.