AUTHOR=Zhou Yuanbing , Ma Jinke , Zhang Ziyu , Niu Xiaodan , Yan Huiyu , Zhang Jun TITLE=AB-Flu nanodrug combined with exercise intervention enhances ROS-mediated antitumor effects in melanoma JOURNAL=Frontiers in Physiology VOLUME=Volume 17 - 2026 YEAR=2026 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2026.1767235 DOI=10.3389/fphys.2026.1767235 ISSN=1664-042X ABSTRACT=PurposeThis study aims to investigate the synergistic effects of AB-Flu nanodrugs and exercise intervention on enhancing the antitumor effects in melanoma by improving the hypoxic tumor microenvironment (TME). The focus is on evaluating how this combination influences reactive oxygen species (ROS) levels, inhibition of melanoma in vivo.MethodsAn intact B16F10 melanoma mouse model was established, and mice were divided into four groups: control, AB-Flu treatment, exercise intervention, and combination therapy (AB-Flu + exercise). AB-Flu nanodrug was administered intraperitoneally, while exercise was facilitated by a weighted swimming intervention. Tumor growth, tumor hypoxia, ROS levels, and apoptosis were analyzed through tumor volume measurements, histological staining, and ROS detection assays. The antitumor effects of different treatments were compared.ResultsThe combination therapy group showed the most significant tumor inhibition efficacy with tumor growth inhibition rates of 56%, compared to 30% for the AB-Flu monotherapy group and 41% for the exercise group. Additionally, tumor tissues from the combination group exhibited significantly lower levels of hypoxia and enhanced tumor cell apoptosis. ROS levels were substantially higher in the combination therapy group compared to other groups, indicating that the combination of AB-Flu and exercise synergistically elevated ROS production, which may contribute to increased tumor cell apoptosis. No significant toxicity was observed in major organs.ConclusionThe combination of AB-Flu nanodrugs and exercise intervention significantly enhances the antitumor effects in melanoma by improving the hypoxic TME, elevating ROS levels, and promoting apoptosis in tumor cells. This strategy may offer a potential approach for melanoma therapy.