2. Academic Validation
  3. Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine

Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine

  • Nat Commun. 2024 Dec 3;15(1):10526. doi: 10.1038/s41467-024-54963-y.
Bowen Wu # 1 2 3,  Zhiqin Wang # 2 4,  Jingyuan Liu 2,  Naishi Li 2,  Xudong Wang 2,  HaoChen Bai 2,  Chunling Wang 2,  Jian Shi 2,  Saiyang Zhang 1,  Jian Song 1,  Yiye Li 5 6,  Guangjun Nie 7 8 9 10
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, PR China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, PR China.
  • 3 Henan Institute of Advanced Technology, Henan, PR China.
  • 4 College of Pharmaceutical Science, Jilin University, Changchun, PR China.
  • 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, PR China. liyy@nanoctr.cn.
  • 6 College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing, PR China. liyy@nanoctr.cn.
  • 7 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, PR China. niegj@nanoctr.cn.
  • 8 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, PR China. niegj@nanoctr.cn.
  • 9 Henan Institute of Advanced Technology, Henan, PR China. niegj@nanoctr.cn.
  • 10 College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing, PR China. niegj@nanoctr.cn.
  • # Contributed equally.
PMID: 39627234 DOI: 10.1038/s41467-024-54963-y
Abstract

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.

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