Abstract
Radiation therapy (RT)-mediated tumor immunogenicity offers an opportunity for synergistic combination RT and immunotherapy. One of the challenges in the clinic is to attain the optimum efficacy of combination RT and immunotherapy with minimized overlapping toxicities. Here, to achieve synergistic therapeutic efficacy of combinational RT and anti-programmed death ligand 1 (aPD-L1) immunotherapy, RT-responsive splintery snowflake-like Au nanocarriers (SAuNC) were synthesized with a method for hierarchical bimetallic supra-nanostructures. Primary Au nanocrystals interconnected with Ag nanocrystals in S-AuNC showed RTresponsive structural deformation resulting in RT-triggered release of cargo aPD-LI in S-AuNC. The local combination of RT and aPD-L1 loaded S-AuNC significantly enhanced the immunogenic cell death for tumor microenvironment conversion. RTtriggered local aPD-L1 release allowed a controlled spatiotemporal combination RT and aPD-L1 immunotherapy resulting in a synergistic anticancer adaptive immune response with minimized systemic immune-related adverse effects.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 13115-13126 |
| Number of pages | 12 |
| Journal | ACS nano |
| Volume | 14 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 27 2020 |
Funding
This work was mainly supported by grants R01CA218659 and R01EB026207 from the National Cancer Institute and National Institute of Biomedical Imaging and Bioengineering. This work was also supported by the Center for Translational Imaging and Mouse Histology and Phenotyping Laboratory at Northwestern University.
Keywords
- Gold nanocarrier
- Image-guided cancer therapy
- Immune-related adverse events
- Immunotherapy
- Localized cancer therapy
- Radiotherapy
ASJC Scopus subject areas
- General Engineering
- General Physics and Astronomy
- General Materials Science
