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

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

Bioactive Materials (Feb 2023)

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

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

Affiliations

Jiangchao Wu: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Xun Wang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Li Chen: Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, China; College of Energy Engineering and State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, China
Jianing Wang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Junlei Zhang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Jianghui Tang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Yongtao Ji: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Jinyuan Song: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Lin Wang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Yaxing Zhao: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Hui Zhang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Taohong Li: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China
Jianpeng Sheng: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China; Corresponding authors. The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China.
Dong Chen: Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, China; College of Energy Engineering and State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, China; Corresponding author. College of Energy Engineering and State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310027, China.
Qi Zhang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China; Corresponding authors. The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China.
Tingbo Liang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310003, China; Corresponding author. The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China.

Journal volume & issue: Vol. 20
pp. 259 – 270

Abstract

Read online

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

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

About the journal

Abstract

Keywords