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Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy.
- Source :
-
Biomaterials . Jan2023, Vol. 292, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds, π–π stacking, and cation–π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 292
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 160784718
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2022.121938