#1311

Nano-Ni0 nanocatalysts disrupt redox homeostasis via hydrogen-induced reductive stress and nickel-driven chemodynamic therapy for bladder cancer treatment and immune modulation

Y. Chiu^1,2,3, L. Yang⁴, Y. Chin⁴, Y. Chen⁴, Y. Tsai⁴, M. Liao⁵, C. Huang^4,6

¹Yangming Branch, Taipei City Hospital, Division of Urology, Department of Surgery, Taipei, Taiwan
²National Yang Ming Chiao Tung University, Department of Urology, College of Medicine and ShuTien Urological Research Center, Taipei, Taiwan
³University of Taipei, Department of Social and Public Affairs, Taipei, Taiwan
⁴National Cheng Kung University, Department of Photonics, Tainan, Taiwan
⁵Department of Applied Chemistry, National Pingtung University, Tainan, Taiwan
⁶National Cheng Kung University, Center of Applied Nanomedicine, Tainan, Taiwan

Introduction:

Bladder cancer remains a major clinical challenge due to high recurrence rates and the limitations of current treatments, such as chemotherapy and radiotherapy, which often cause severe side effects. A major obstacle in cancer therapy is the redox adaptability of tumor cells, allowing them to survive oxidative stress.

Material and methods:

Nano-Ni0 was synthesized via hydrothermal method and characterized for its structure and catalytic properties. Hydrogen release was analyzed by gas chromatography (GC), while nickel ion release under acidic conditions was quantified by atomic absorption spectroscopy (AAS). Cellular assays evaluated ROS modulation, oxidative damage, autophagy induction, and cell viability in T24 cells. Reductive stress, immunogenic cell death (ICD) markers, and mcrophage polarization was examined.

Results:

Nano-Ni0 demonstrated a hydrogen release in acidic conditions and catalyzed H2O2 to generate •OH (chemodynamic therapy (CDT) that caused mitochondrial dysfunction, DNA damage, and autophagy-related cell death. Furthermore, nano-Ni0 treatment triggered ICD, as evidenced by increased CRT exposure on the cancer cell membrane and enhanced extracellular release of HMGB1, signaling immune activation. Additionally, nano-Ni0-treated cancer cells promoted macrophage polarization toward an M1 phenotype, further amplifying anti-tumor immune responses.