2. Academic Validation
  3. Development of AuxCuyPdz Nanocomposites as Therapeutic Agents: Enhancing Cancer Treatment through Autophagy Modulation and Immune-Associated Effects

Development of AuxCuyPdz Nanocomposites as Therapeutic Agents: Enhancing Cancer Treatment through Autophagy Modulation and Immune-Associated Effects

  • ACS Appl Mater Interfaces. 2026 Mar 18;18(10):14540-14557. doi: 10.1021/acsami.5c20536.
Li-Xing Yang 1 2,  Yi-Chun Chiu 3 4 5 6,  Yi-Lun Chen 7,  Ting-Ying Chen 7,  Yi-Tseng Tsai 1 2,  Yu-Cheng Chin 1 2,  Ya-Ling Yeh 8,  Ying-Jan Wang 8,  Chih-Chia Huang 1 2 9,  Rong-Jane Chen 8 10,  Mei-Yi Liao 7
Affiliations

Affiliations

  • 1 Department of Photonics, National Cheng Kung University, Tainan 701, Taiwan.
  • 2 Center of Applied Nanomedicine and Core Facility Center, National Cheng Kung University, Tainan 701, Taiwan.
  • 3 Division of Urology, Department of Surgery, Yangming Branch, Taipei City Hospital, Taipei 111, Taiwan.
  • 4 Department of Urology, College of Medicine and Shu-Tien Urological Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 5 Department of Health and Welfare, University of Taipei, Taipei 111, Taiwan.
  • 6 Department of Social and Public Affairs, University of Taipei, Taipei 111, Taiwan.
  • 7 Department of Applied Chemistry, National Pingtung University, Pingtung 900, Taiwan.
  • 8 Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
  • 9 Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 10 Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
PMID: 41778422 DOI: 10.1021/acsami.5c20536
Abstract

The development of multimetallic nanoparticles for Cancer treatment represents a significant advancement in the field of nanomedicine. We introduce a Cu-templated synthesis method to create AuxCuyPdz hollow nanomicrostructures, wherein gold atoms stabilize copper (Cu) and facilitate the incorporation of palladium (Pd) through oxidation and coreduction processes. These ternary nanocomposites demonstrate enhanced cellular uptake via the copper transporter CTR1/2-mediated pathway and exhibit superior catalytic activity for the reaction of hydrogen peroxide to generate hydroxyl radicals. The presence of both Cu and Pd triggers significant autophagic responses, increases lipid peroxidation, and disturbs copper metabolism, as indicated by the increased expression of autophagy-related proteins and mitochondrial Reactive Oxygen Species, ultimately leading to selective Cancer cell death. The synergistic effects of these three metals not only increase Autophagy but also promote the degradation of immune escapable proteins, including IDO1, PD-L1, and CD47. Based on the Cu/Pd element-induced biochemical stimulation, we conducted a proof-of-concept in vivo validation using a murine orthotopic bladder tumor model to demonstrate that Au-Cu-Pd ternary nanoparticles enhance Autophagy and Ferroptosis, thereby reversing the immunosuppressive tumor microenvironment by reducing immune escape proteins. These effects increased the infiltration of antitumor immune cells, with further enhancement from photothermal therapy at a low laser power density and sample dose. Our findings offer valuable insights into designing multimetallic nanoparticles through element chemistry for Cancer therapy, highlighting their potential as effective modulators of Autophagy.

Keywords

alloy nanoparticles; autophagy modulation; cancer-selective therapy; ferroptosis; immunoregulation; metal-based nanomedicine; multimetallic nanocomposites.

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