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Review Open Access

Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review)

  • Authors:
    • Zhefei Du
    • Zhenyu Cao
    • Chao Fang
    • Daihan Xie
    • Lixin Xie
    • Chunxia Su
    • Yu Huo
  • View Affiliations / Copyright

    Affiliations: Department of Comprehensive Oncology Center, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, School of Medicine, Tongji University, Shanghai 200433, P.R. China, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, Guangxi 530222, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 2
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    Published online on: November 4, 2025
       https://doi.org/10.3892/ijo.2025.5815
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Abstract

Transition‑metal nanoparticles (NPs) have been extensively studied owing to their unique physical and chemical properties, ability to form a variety of nanostructures and targeting properties. After surgery, chemotherapy, radiotherapy and targeted therapy, immunotherapy has emerged as a major strategy for cancer treatment. In particular, immune checkpoint inhibition has attracted much attention in preclinical and clinical applications. The combination of transition‑metal NPs with tumor immunotherapy offers great potential. Therefore, the present review focused on four major transition‑metal NPs (Au, Ag, Cu and Fe NPs) and their respective categories, presented their characteristics and roles in the biomedical field and discussed their potential toxicities. In addition, the mechanisms of action of different tumor immunotherapies and the applications of transition‑metal NPs in tumor immunotherapy are discussed. The current status of, and challenges associated, with the clinical transformation of transition‑metal NPs in tumor immunotherapy are described to provide ideas for the subsequent development and clinical application of transition‑metal NPs.
View Figures

Figure 1

The different shapes of AuNPs. (A)
Gold nanospheres. (B) Gold nanorods. (C) Gold nanoplates. (D) Gold
nanocages. (E) Gold nanotriangles. (F) Gold nanostars. (G) Gold
nanoflowers. AuNPs, gold nanoparticles.

Figure 2

Antibacterial mechanism of Cu-based
NPs. Cu-based NPs are capable of damaging the cell walls. At the
same time, they are internalized in bacterial cells, releasing
Cu2+, leading to ROS accumulation and oxidative stress,
which can damage mitochondria and DNA. Cu, copper; NPs,
nanoparticles; ROS, reactive oxygen species.

Figure 3

Schematic illustration of the
synthesis and function of cancer vaccine formulation encapsulating
OVA antigen. Upon administration, the nano-vaccine migrates to
lymph nodes, promoting DC maturation and enhancing antigen
cross-presentation. This process activates a durable anti-tumor
T-cell immune response for protection against melanoma. OVA,
ovalbumin; DCs, dendritic cells.

Figure 4

Mechanism of MDP NPs-induced
immunogenic cell death synergizing with anti-PD-1 therapy for tumor
suppression. This schematic illustration depicts a phenolic
immunogenic cell death nano-inducer designed to sensitize tumors to
anti-PD-1 checkpoint blockade immunotherapy and its underlying
immune mechanisms. It first presents the self-assembly process
forming MDP NPs. Subsequently, a mouse bilateral tumor model
demonstrates the evaluation of these NPs combined with PD-1
blockade for tumor inhibition and elucidates their immune
mechanisms. MDP NPs, metal-doxorubicin-phenolic nanoparticles;
PD-L1, programmed cell death ligand 1; NPs, nanoparticles; PEG,
polyethylene glycol; DOX, doxorubicin; CTL, cytotoxic T lymphocyte;
DC, dendritic cell; ICD, immunogenic cell death.

Figure 5

Mechanism of triple-kill tumor
eradication synergized with immunotherapy via metal-phenolic
network nanopumps (AHSC NPs). This schematic illustrates the
preparation of AHSC NPs and their triple therapeutic strategy for
tumor eradication. The nanopumps were synthesized via the
self-assembly of Hf coordinated with Ce6-PEG-polyphenols,
atovaquone and sabutoclax. Within this system, Hf acts as a
radiosensitizer to enhance radiation efficacy; the photosensitizer
Ce6 conjugated to PEG is activated by the inelastic scattering of
photoelectrons generated from X-ray energy transferred by Hf,
thereby boosting ROS production; sabutoclax targets the apoptotic
signaling pathway to promote the activation of downstream apoptotic
proteins, increasing tumor cell death; and atovaquone regulates
mitochondrial function to liberate more oxygen within the tumor
microenvironment, which is crucial for alleviating radioresistance.
Furthermore, the strategy incorporates two antibodies (anti-CTLA-4
and anti-PD-L1) to trigger a potent immune response at the tumor
site, enabling immune recognition while suppressing PD-L1
expression on tumor cells, thereby amplifying therapeutic efficacy.
Notably, tumor-associated antigens can be internalized by receptors
on APCs, invoking a robust immune response. AHSC NPs,
atovaquone-hafnium-sabutoclax-Ce6 nanoparticles; Hf, hafnium; PEG,
polyethylene glycol; ROS, reactive oxygen species; CTLA-4,
cytotoxic T lymphocyte antigen-4; PD-L1, programmed cell death
ligand 1; APCs, antigen-presenting cells; TCR, T cell receptor;
MHC, major histocompatibility complex.

Figure 6

Graphical summary of the present
review. Au, gold; Ag, silver; Cu, copper; Fe, iron; PD-L1,
programmed cell death ligand 1; PD-1, programmed death receptor-1;
TNFR, tumor necrosis factor receptor; APC, antigen-presenting cell;
ICOS, inducible T-cell costimulator; ICOSLG, inducible T-cell
costimulator ligand.
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Copy and paste a formatted citation
Spandidos Publications style
Du Z, Cao Z, Fang C, Xie D, Xie L, Su C and Huo Y: Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review). Int J Oncol 68: 2, 2026.
APA
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., & Huo, Y. (2026). Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review). International Journal of Oncology, 68, 2. https://doi.org/10.3892/ijo.2025.5815
MLA
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., Huo, Y."Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review)". International Journal of Oncology 68.1 (2026): 2.
Chicago
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., Huo, Y."Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review)". International Journal of Oncology 68, no. 1 (2026): 2. https://doi.org/10.3892/ijo.2025.5815
Copy and paste a formatted citation
x
Spandidos Publications style
Du Z, Cao Z, Fang C, Xie D, Xie L, Su C and Huo Y: Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review). Int J Oncol 68: 2, 2026.
APA
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., & Huo, Y. (2026). Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review). International Journal of Oncology, 68, 2. https://doi.org/10.3892/ijo.2025.5815
MLA
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., Huo, Y."Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review)". International Journal of Oncology 68.1 (2026): 2.
Chicago
Du, Z., Cao, Z., Fang, C., Xie, D., Xie, L., Su, C., Huo, Y."Cancer immunotherapy strategies based on transition‑metal medical materials: Still a long way to go (Review)". International Journal of Oncology 68, no. 1 (2026): 2. https://doi.org/10.3892/ijo.2025.5815
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