Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy characterized by dysregulated energy and stromal metabolism. It is strongly supported by activated pancreatic stellate cells (PSC) which drive excessive desmoplasia and tumor growth via metabolic crosstalk. Herein, a programmed nanosystem is designed to dual rectify the metabolism abnormalities of the PDAC cells, which overexpress glucose transporter 1(GLUT1) and CD71, and the PSC for oncotherapy. The nanosystem is based on a tumor microenvironment-responsive liposome encapsulating an NF-κB inhibitor (TPCA-1) and a CD71 aptamer-linked Glut1 siRNA. TPCA-1 reverses the activated PSC to quiescence, which hampers metabolic support of the PSC to PDAC cells and bolsters the PDAC cell-targeting delivery of the siRNA. Aerobic glycolysis and the following enhancement of oxidative phosphorylation are restrained by the nano-modulation so as to amplify anti-PDAC efficacy in an orthotopic xenograft mouse model, which implies more personalized PDAC treatment based on different energy metabolic profiles.
Authors
- Jian Shi (ORCID: https://orcid.org/0000-0002-0481-3442)
- Sai‐Yang Zhang (ORCID: https://orcid.org/0000-0003-4395-8879)
- Zhiqin Wang (ORCID: https://orcid.org/0000-0002-1708-7689)
- Yiye Li (ORCID: https://orcid.org/0000-0001-9396-2345)
- Guangjun Nie (ORCID: https://orcid.org/0000-0001-5040-9793)
- H. F. Bai
- Bowen Wu (ORCID: https://orcid.org/0000-0003-1759-9729)
- Naishi Li (ORCID: https://orcid.org/0000-0002-2261-7349)
- Xudong Wang (ORCID: https://orcid.org/0000-0002-3522-3971)
- Chunling Wang (ORCID: https://orcid.org/0000-0002-8622-8465)
- Jingyuan Liu (ORCID: https://orcid.org/0000-0001-5624-1258)
- Jian Song (ORCID: https://orcid.org/0000-0001-6767-2643)
Institutions
- Jilin University (CN)
- Henan University of Technology (CN)
- Zhengzhou University (CN)
- Henan Institute of Technology (CN)
- Henan Communication Science and Technology Research Institute (China) (CN)
- National Center for Nanoscience and Technology (CN)
- Henan Institute of Science and Technology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-03
- DOI
- https://doi.org/10.1038/s41467-024-54963-y
- Citations
- 16
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 4.52
Funders
- National Key Research and Development Program of China