Binary mineral nanoparticles enable intravascular delivery of metal ions to tumors for metalloimmunotherapy.
| Title: | Binary mineral nanoparticles enable intravascular delivery of metal ions to tumors for metalloimmunotherapy. |
|---|---|
| Authors: | Nguyen BL; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Le ND; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Nguyen TOO; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Ahn D; School of Mechanical Engineering, Soongsil University, Seoul, Republic of Korea.; Patil BR; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Kim B; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Phung CD; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Pham DV; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Lee JM; School of Mechanical Engineering, Soongsil University, Seoul, Republic of Korea.; Hong J; School of Mechanical Engineering, Soongsil University, Seoul, Republic of Korea.; Chang JH; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.; Ku SK; College of Korean Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.; Kim J; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. jeonghwankim@yu.ac.kr.; Kim JO; College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. jongohkim@yu.ac.kr. |
| Source: | Nature communications [Nat Commun] 2026 Jan 12; Vol. 17 (1), pp. 1556. Date of Electronic Publication: 2026 Jan 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Immunotherapy*/methods ; Calcium*/administration & dosage ; Calcium*/chemistry ; Nanoparticles*/chemistry ; Nanoparticles*/administration & dosage ; Sodium*/administration & dosage ; Sodium*/chemistry ; Neoplasms*/immunology ; Neoplasms*/drug therapy ; Neoplasms*/therapy; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/pharmacology ; Drug Delivery Systems/methods ; Animals ; Humans ; Mice ; Cell Line, Tumor ; Ions ; Female ; Hydrogen-Ion Concentration ; Mice, Inbred C57BL |
| Abstract: | Although disruptions in metal ion homeostasis leading to severe cellular damage and regulated cell death are a promising strategy for cancer immunotherapy, challenges in overloading these ions to tumor cells without premature release have limited their therapeutic applications. In this study, we develop binary mineral nanoparticles incorporating both Ca2+ and Na+ ions to enhance the cytotoxic effects of ion interference in cancer immunotherapy. Engineered using a microfluidic system for uniform size distribution and scalability, these nanoparticles exhibit pH-sensitive ion release. Systemically administered, they preferentially accumulate in tumors, elevating intracellular Ca2+ and Na+ levels and inducing immunogenic cell death without calcium channel activators or other small-molecule inducers. Our binary mineral nanoparticles significantly enhance antitumor immunity, especially when combined with an immune checkpoint inhibitor, leading to long-term immunity and inhibition of metastasis. This nanotechnology-enabled synergistic delivery of Ca²⁺ and Na⁺ ions represents a promising adjunct to existing metalloimmunotherapy strategies for cancer eradication.; (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
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| Grant Information: | RS-2022-NR070844 National Research Foundation of Korea (NRF); RS-2024-00343765 National Research Foundation of Korea (NRF); RS-2025-14292970 National Research Foundation of Korea (NRF); RS-2025-02303064 National Research Foundation of Korea (NRF) |
| Substance Nomenclature: | SY7Q814VUP (Calcium); 9NEZ333N27 (Sodium); 0 (Ions); 0 (Immune Checkpoint Inhibitors) |
| Entry Date(s): | Date Created: 20260112 Date Completed: 20260211 Latest Revision: 20260214 |
| Update Code: | 20260214 |
| PubMed Central ID: | PMC12895034 |
| DOI: | 10.1038/s41467-025-68279-y |
| PMID: | 41526370 |
| Database: | MEDLINE |
Journal Article