Bimetallic nanoadjuvants for cancer vaccines

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 46; no. 10; pp. 958 - 974
• Main Authors: Luo, Jiangqi, Wang, Yue, Yu, Chengzhong, Yang, Yannan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2025
• Subjects: adjuvant; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacology; Advanced Basic Science; Animals; cancer vaccine; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Humans; immunotherapy; metal-based nanoparticle; Neoplasms - immunology; Neoplasms - therapy; metal-based nanoparticle; cancer vaccine; adjuvant; immunotherapy
• ISSN: 0165-6147; 1873-3735; 1873-3735
• DOI: 10.1016/j.tips.2025.08.007

Metal ions have emerged as promising candidates for constructing adjuvants for cancer vaccine due to their unique immune modulation activities.Bimetallic nanoadjuvants (BMNAs) synergistically activate multiple immune signaling pathways, such as GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) and NLR family pyrin domain containing 3 (NLRP3), overcoming limitations of single-metal adjuvants for enhanced T cell responses in cancer vaccines.Strategic selection of metal pairings in BMNAs can lead to controlled ion release, optimized pharmacokinetics and biosafety, enhanced antigen cross-presentation, and promoted immune activation, yielding superior antitumor efficacy in preclinical models.Aluminum salts (alum) and calcium phosphate were clinically approved as adjuvants in the last century, and an increasing number of metal ions, such as manganese, are now entering clinical trials, highlighting the strong potential of BMNAs for clinical translation. Adjuvants are substances used in vaccines to boost antigen-specific immune responses. Aluminum salts (alum) were the first adjuvant approved for human use. Unfortunately, they mainly induce antibody responses and are ineffective at eliciting strong T cell immunity, limiting their use in cancer vaccines. Recent advances reveal the mechanisms of various metal ions in modulating immune signaling. By integrating the synergistic immunomodulation of metal ion pairings with nanotechnology, bimetallic nanoadjuvants (BMNAs) are revolutionizing cancer vaccine. This approach overcomes the limitation of conventional single metal adjuvants by enabling multiplexed immune activation, leading to robust T cell responses for tumor control. This review highlights the immunological mechanisms of metal ions, the rationale behind their pairing in BMNAs, and current challenges for clinical translation. Adjuvants are substances used in vaccines to boost antigen-specific immune responses. Aluminum salts (alum) were the first adjuvant approved for human use. Unfortunately, they mainly induce antibody responses and are ineffective at eliciting strong T cell immunity, limiting their use in cancer vaccines. Recent advances reveal the mechanisms of various metal ions in modulating immune signaling. By integrating the synergistic immunomodulation of metal ion pairings with nanotechnology, bimetallic nanoadjuvants (BMNAs) are revolutionizing cancer vaccine. This approach overcomes the limitation of conventional single metal adjuvants by enabling multiplexed immune activation, leading to robust T cell responses for tumor control. This review highlights the immunological mechanisms of metal ions, the rationale behind their pairing in BMNAs, and current challenges for clinical translation.