机构：[1]State Key Laboratory of Advanced Fiber Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.[2]State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.[3]Department of Ultrasound, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai 200336, China.
Due to the hypoxic and immunosuppressive tumor microenvironment, pancreatic cancer is poorly responsive to immunotherapy. Cytokines offer a good occasion to reinforce immune responses via overcoming immunotherapy resistance, but their short half-life and unbridled biodistribution often limit their therapeutic effects and cause off-tumor adverse effects. In this study, an oxygen-delivering semiconducting polymer nanocytokine is designed for sono-induced combination immunotherapy of orthotopic pancreatic cancer. Such a nanocytokine (SPNI) is constructed based on the sonodynamic semiconducting polymer as a skeleton, which is loaded with an oxygen carrier, perfluorohexane (PFH), and conjugation of interleukin-12 (IL-12) via a singlet oxygen (1O2)-cuttable thioketal (TK) fragment. Via enriching into orthotopic pancreatic tumor sites, SPNI delivers oxygen to relieve tumor hypoxia, which greatly amplifies the sonodynamic therapy (SDT) efficacy with ultrasound treatment, and also immunogenic cell death is triggered. More importantly, SPNI precisely delivers IL-12 into orthotopic pancreatic tumor sites via the severing of the TK fragments by the generated 1O2, resulting in the activation of strong antitumor immune responses. Such a sono-induced combination immunotherapy of SPNI exhibits an amplified efficacy in eradicating orthotopic pancreatic cancer and inhibiting tumor metastasis, thus offering a promising program for cancer therapy.
基金：
the National Natural Science
Foundation of China (52203155 and 52311530771) and
Donghua University 2024 Cultivation 798 Project of Discipline
Innovation.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类|2 区材料科学
小类|2 区材料科学：综合2 区纳米科技
最新[2025]版：
大类|2 区材料科学
小类|2 区材料科学：综合2 区纳米科技
第一作者：
第一作者机构：[1]State Key Laboratory of Advanced Fiber Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhan Yiduo,Li Fei,Wang Fengshuo,et al.Oxygen-Delivering Semiconducting Polymer Nanocytokines for Sono-Induced Combination Immunotherapy of Orthotopic Pancreatic Cancer[J].ACS Applied Materials & Interfaces.2025,doi:10.1021/acsami.5c15319.
