School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, 637457, Singapore, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, 636921, Singapore, Singapore.
Angew Chem Int Ed Engl. 2024 Jul 22;63(30):e202405358. doi: 10.1002/anie.202405358. Epub 2024 Jun 19.
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 O-cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe generates O 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.
嗜酸性粒细胞是影响 T 细胞介导的抗肿瘤免疫的重要免疫效应细胞。然而，嗜酸性粒细胞的低频和受限活性限制了癌症免疫疗法的效果。我们在此报告了一种嗜酸性粒细胞激活的半导体聚合物纳米颗粒 (SPNe)，以提高光动力肿瘤免疫原性，调节嗜酸性粒细胞趋化性，并重新激活 T 细胞免疫，用于激活的癌症光免疫治疗。SPNe 由两亲性半导体聚合物和二肽基肽酶 4 (DPP4) 抑制剂西他列汀通过 O-可裂解硫缩酮键合而成。局部近红外光照射后，SPNe 产生 O 以引发肿瘤的免疫原性细胞死亡，并诱导 sitagliptin 的特异性激活。随后抑制 DPP4 可增加肿瘤内 CCL11 水平，促进嗜酸性粒细胞趋化和激活。SPNe 介导的光免疫疗法与免疫检查点阻断协同作用，极大地促进了嗜酸性粒细胞和 T 细胞的浸润和激活，有效抑制了肿瘤生长和转移。因此，本研究提出了一种通用的聚合物纳米平台，用于调节特异性免疫细胞，以实现精准癌症免疫治疗。
