Abstract
Targeted delivery of immunomodulatory molecules to the lymph nodes is an attractive means of improving the efficacy of anti-cancer immunotherapy. In this study, to improve the efficacy of PD-1 blockade-based therapy, nanocages were designed by surface engineering to decorate a programmed cell death protein 1 (PD-1) that is capable of binding against programmed death-ligand 1 (PD-L1) and -ligand 2 (PD-L2). This nanocage-mediated multivalent interaction remarkably increases the binding affinity and improves the antagonistic activity compared to free soluble PD-1. In addition, with the desirable nanocage size for optimal tumor-draining lymph node (TDLN) targeting (approximately 20 nm), rapid draining and increased accumulation into the TDLNs were observed. Moreover, the interference of the PD-1/PD-L axis with ultra-high affinity in the tumor microenvironment (effector phase) and the TDLNs (cognitive phase) significantly enhances the dendritic cell-mediated tumor-specific T cell activation. This characteristic successfully inhibited tumor growth and induced complete tumor eradication in some mice. Thus, the delivery of immunomodulatory molecules with nanocages can be a highly efficient strategy to achieve stronger anti-tumor immunity.
Original language | English |
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Pages (from-to) | 328-338 |
Number of pages | 11 |
Journal | Journal of Controlled Release |
Volume | 333 |
DOIs | |
Publication status | Published - 2021 May 10 |
Bibliographical note
Publisher Copyright:© 2021 The Author(s)
Keywords
- Drug delivery
- Nanocage
- PD-1/PD-L blockade
- Surface engineering
- Tumor-draining lymph node
ASJC Scopus subject areas
- Pharmaceutical Science