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A photo-activable nano-agonist for the two-signal model of T cell in vivo activation.

Authors :
You, Yuchan
Jin, Feiyang
Du, Yan
Zhu, Luwen
Liu, Di
Zhu, Minxia
Du, Yuyin
Lang, Jialu
Li, Weishuo
Ji, Jian-Song
Du, Yong-Zhong
Source :
Journal of Controlled Release. Sep2023, Vol. 361, p681-693. 13p.
Publication Year :
2023

Abstract

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e. , signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy. [Display omitted] • A photo-activable nano-agonist for T cell in vivo activation to achieve tumor suppression with safety. • Photo-clustering of activatory receptors on the cell surface improves the activation and expansion of T cells. • A chemical tool to manipulate cell behavior in situ which can be easily tailored for other therapies. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01683659
Volume :
361
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
171829950
Full Text :
https://doi.org/10.1016/j.jconrel.2023.08.033