Magnetic thermoradiotherapy for lung cancer: evaluation in A549-based preclinical models

Radiotherapy is a cornerstone in lung cancer management; however, achieving effective tumor eradication while sparing surrounding healthy tissue remains a major clinical challenge. Recent advances in nanotechnology offer new opportunities to enhance radiotherapeutic precision and efficacy through improved tumor targeting, increased dose deposition, and integration of complementary treatment modalities such as magnetic fluid hyperthermia (MFH). This study evaluates a novel strategy combining X-ray irradiation, MFH, and engineered magnetic nanoparticles to improve treatment efficacy in lung cancer.

Carbon-encapsulated iron nanoparticles (Fe@C), coated with polyethyleneimine (PEI) and functionalized with a monoclonal IgG antibody targeting the β3 subunit (CD61) of the αvβ3 integrin receptor, were loaded with glucose oxidase (GOX) to produce Fe@C-PEI-IgG-GOX nanoparticles. These nanoparticles were used to sensitize lung cancer cells prior to radiotherapy in combination with magnetic fluid hyperthermia induced by iron oxide nanoparticles exposed to an alternating magnetic field. Therapeutic efficacy was evaluated using human adenocarcinomic alveolar basal epithelial cells (A549) in both in vitro and in vivo models, including A549 cell cultures and NUDE Balb/c mice bearing A549 xenograft tumors.

The engineered Fe@C-PEI-IgG-GOX nanoparticles significantly reduced lung cancer cell viability in vitro, consistent with the known enzymatic activity of glucose oxidase, which catalyzes the oxidation of glucose to gluconic acid with concomitant hydrogen peroxide generation. This process negatively affected cancer cell survival, induced DNA damage, and suppressed colony formation. In vivo, the combination of radiotherapy and magnetic fluid hyperthermia applied together with a GOX-containing, anti-CD61-functionalized magnetic nanoplatform was associated with improved therapeutic outcomes in the lung cancer model. This multimodal approach resulted in enhanced therapeutic efficacy and prolonged time to the protocol-defined endpoint.

Overall, these findings highlight the promise of a GOX-based, targeted magnetic nanoplatform combined with radiotherapy and magnetic fluid hyperthermia as an effective multimodal strategy for lung cancer treatment, warranting further preclinical optimization and mechanistic studies. Importantly, the observed therapeutic benefit reflects the overall outcome of the combined treatment in the in vivo model, and the relative contributions or potential interactions among the individual treatment modalities were not mechanistically dissected in this study.