Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma

• DOI: 10.1016/j.bioactmat.2022.05.022
• Publication Date: 2022-06-02T21:56:39Z
• Authors: Jiangchao Wu; Xun Wang; Li Chen; Jianing Wang; Junlei Zhang; Jianghui Tang; Yongtao Ji; Jinyuan Song; Lin Wang; Yaxing Zhao; Hui Zhang; Taohong Li; Jianpeng Sheng; Dong Chen; Qi Zhang; Tingbo Liang
• Keywords: Hypoxia; Tumor Hypoxia; Immune checkpoint

Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing expression immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy improve validity checkpoint blockade (ICB).Here, we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization, bioavailability, and biocompatibility direct delivery into sites by interfacial polymerization.We observed enhanced concentration hypoxia environment maintained long period both vitro vivo. We found that could significantly efficiency ICB against PDAC Mechanismly, combined treatments using reduce infiltration tumor-associated macrophages (TAMs) polarized pro-tumor M2 anti-tumor M1 macrophages. In addition, elevate proportion T helper subtype 1 cells (Th1 cells) cytotoxic lymphocytes (CTLs) mediate response TME.In summary, this pre-clinical study indicated reversing was effective performances on PDAC, which holds great treating future.