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Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors.
- Source :
-
Nature biotechnology [Nat Biotechnol] 2024 Oct 24. Date of Electronic Publication: 2024 Oct 24. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Strategies to enhance the anti-tumor immune response of stereotactic ablative radiotherapy (SABR) at primary tumors and abscopal sites are under intensive investigation. Here we report a metabolizable binary supracluster (BSC <subscript>gal</subscript> ) that combines gold nanoclusters as radiosensitizing adjuvants with small interfering RNA (siRNA) targeting the immunosuppressive mediator galectin-1 (Gal-1). BSC <subscript>gal</subscript> comprises reversibly crosslinked cationic gold nanoclusters and siRNA complexes in a polymer matrix that biodegrades over weeks, facilitating clearance (90.3% in vivo clearance at 4 weeks) to reduce toxicity. The particle size well above the renal filtration threshold facilitates passive delivery to tumors. Using mouse models of head and neck cancer, we show that BSC <subscript>gal</subscript> augments the radiodynamic and immunotherapeutic effects of SABR at the primary and metastatic tumors by promoting tumor-inhibitory leukocytes, upregulating cytotoxic granzyme B and reducing immunosuppressive cell populations. It outperforms SABR plus Gal-1 antagonists, chemoradiation drug cisplatin or PD-1 inhibitor. This work presents a translatable strategy to converge focal radiosensitization with targeted immune checkpoint silencing for personalized radioimmunotherapy.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Details
- Language :
- English
- ISSN :
- 1546-1696
- Database :
- MEDLINE
- Journal :
- Nature biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 39448881
- Full Text :
- https://doi.org/10.1038/s41587-024-02448-0