Results
Title

Eosinophil‐Activating Semiconducting Polymer Nanoparticles for Cancer Photo‐Immunotherapy.

Authors

Zhang, Chi; Huang, Jingsheng; Xu, Mengke; Yu, Jie; Wei, Xin; He, Shasha; Pu, Kanyi

Abstract

Eosinophils are important immune effector cells that affect T cell‐mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the outcome of cancer immunotherapies. We herein report an eosinophil‐activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T‐cell immunity for activated cancer photo‐immunotherapy. SPNe comprises an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2‐cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe generates 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe‐mediated photo‐immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

Subjects

CD26 antigen; T cells; CELL death; POLYMERS; CELLULAR immunity; EOSINOPHILS

Publication

Angewandte Chemie, 2024, Vol 136, Issue 30, p1

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202405358