Pancreatic cancer is among the deadliest malignancies, with few treatment options for locally advanced, unresectable cases. Conventional therapies, such as chemoradiotherapy and hyperthermia, show promise but face challenges in improving outcomes. This study introduces a novel drug delivery system using gemcitabine (GEM)-loaded layer-by-layer magnetic nanoparticles (LBL MNPs) combined with alternating magnetic field (AMF) application and X-ray irradiation to enhance therapeutic efficacy. LBL MNPs were synthesized using optimized layering techniques to achieve superior drug loading and controlled release. Human pancreatic cancer cells (PANC-1) were treated with LBL MNPs alone, with AMF-induced hyperthermia, and in combination with X-rays. The results demonstrate that the 7-layer LBL MNPs exhibited optimal cytotoxicity, significantly reducing cell viability at concentrations of 30 µg/mL and higher. Combining 7-layer LBL MNPs with AMF increased cell death in a time- and concentration-dependent manner, achieving up to 98% inhibition of cell proliferation. The addition of X-rays to the regimen demonstrated a strong synergistic effect, resulting in a 13-fold increase in cell death compared to controls. These findings highlight the potential of this integrated approach to improve outcomes in patients with pancreatic cancer.

This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, R, and CiteSpace. China emerged as the leading contributor, accounting for 1051 publications (50.41%), followed by the USA. Liu Zhuang is the most productive author in this field. American Chemical Society (ACS) Nano published the most influential articles and accumulated the highest number of citations. Advanced Targeted Therapies in Cancer: Drug Nanocarriers, the Future of Chemotherapy was the most cited, with 1255 citations. Citation bursts have revealed emerging research trends in targeted delivery, cellular studies, co-delivery strategies, immunogenic cell death, polymeric nanoparticles, tumor research, and drug delivery systems, indicating potential avenues for future research. Over the past two decades, nanomaterials for radiotherapy have gained substantial attention. Key areas of focus include enhancing the efficacy of radiotherapy, achieving targeted drug delivery, minimizing adverse effects, and integrating nanomaterials with other therapeutic modalities. Future investigations are expected to improve the precision of radiotherapy, augment radiation effects, and optimize the tumor microenvironment.