Eosinophil‐Activating Semiconducting Polymer Nanoparticles for Cancer Photo‐Immunotherapy

Author:

Zhang Chi1,Huang Jingsheng1,Xu Mengke1,Yu Jie1,Wei Xin1,He Shasha1,Pu Kanyi12ORCID

Affiliation:

1. School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University 70 Nanyang Drive 637457 Singapore Singapore

2. Lee Kong Chian School of Medicine Nanyang Technological University 59 Nanyang Drive 636921 Singapore Singapore

Abstract

AbstractEosinophils 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.

Publisher

Wiley

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