Synthesis of Covalently Linked Bismuthene-Graphene Heterostructure Loaded with Mitomycin C for Combined Radio-thermo-chemotherapy of Triple-Negative Breast Cancer

Abstract

The fabrication of innovative nanomaterials for cancer treatment is essential for reducing its morbidity. The present study focuses on the synthesis, evaluation, and utilization of bismuth nanosheet-reduced graphene oxide (BiNS-rGO) heterostructure as a platform for cancer combination therapy. 4-aminothiophenol (4-ATP) was applied to improve the rGO biocompatibility and functionality following its synthesis through a straightforward liquid-phase exfoliation technique. The successful fabrication of the heterostructure with regulated thickness and morphology was confirmed by structural characterization using Fourier transform infrared spectroscopy, atomic force microscopy, scanning transmission electron microscopy, and X-ray diffraction. Following the evaluation of the photothermal characteristics of the BiNS-rGO heterostructure, it was found that light-to-heat conversion of η=67.6% was efficient under near-infrared (NIR) laser irradiation. The heterostructure demonstrated excellent photothermal stability and recyclability, making it highly promising for photothermal treatment (PTT) applications. Drug loading and release studies revealed that the anticancer drug mitomycin C (MitoC) can be loaded efficiently and released in a pH-responsive manner, underscoring its potential for controlled drug delivery. The toxic effects of BiNS-rGO heterostructure on breast cancer cells (MDA-MB-231) both alone and in combination with MitoC, PTT, and radiation (RT) were evaluated through in vitro studies employing the MTT assay. The combined therapy's positive effects on cancer cells were demonstrated by increased cytotoxicity and apoptotic induction, demonstrating the complementary roles of BiNS-rGO mediated PTT and RT. Furthermore, elevation of apoptotic genes, specifically caspase-3, was found by real-time quantitative polymerase chain reaction (qRT-PCR) research, facilitating the induction of cancer cell death. Overall, this research demonstrates the potential of the BiNS-rGO heterostructure as a versatile nano platform for combination cancer therapy that combines radiation, controlled drug delivery, and photothermal therapy with maximum efficacy with minimal side effects. This research study creates new opportunities for the development of sophisticated nanomaterials for targeted cancer therapy.