Enzymatically responsive nanocarriers targeting PD-1 and TGF-β pathways reverse immunotherapeutic resistance and elicit robust therapeutic efficacy.

• Tác giả: Anni Chen, Chunhua Li, Rutian Li, Baorui Liu, Qin Liu, Fanyan Meng, Xiaoping Qian, Yuling Qiu, Jie Shao, Chun Wang, Qin Wang, Ying-Tzu Yen, Lixia Yu, Zhifan Zhang
• Ngôn ngữ: eng
• Ký hiệu phân loại: 979.704 Statehood period, 1889-
• Thông tin xuất bản: England : Journal of nanobiotechnology , 2025
• Bộ sưu tập: NCBI
• ID: 469454

Tóm tắt

Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment, yet resistance remains a challenge. Co-inhibition of PD-1/PD-L1 and TGF-β shows promise but faces limited efficacy and systemic toxicity. We developed gelatinase-responsive nanoparticles (GPNPs) delivering anti-PD-1 antibody (αPD-1) and TGF-β receptor I inhibitor galunisertib (Gal). GPNPs effectively inhibit tumor progression without observed side effects. Immune profiling by cytometry assay reveals robust recruitment of both activated and exhausted tumor-infiltrating lymphocytes (TILs) and macrophages. Transcriptomic analysis indicates extracellular matrix modulation, supported by reduced collagen deposition and αSMA expression. Fate mapping demonstrates attenuation of Pdgfrα