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Nature Communications

Nature Communications

IF: 14.69
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Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine

Published:3 December 2024 DOI: 10.1038/s41467-024-54963-y
Bowen Wu, Zhiqin Wang, Jingyuan Liu, Naishi Li, Xudong Wang, HaoChen Bai, Chunling Wang, Jian Shi, Saiyang Zhang, Jian Song, Yiye Li, Guangjun Nie

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.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Dimethyl sulfoxide 67-68-5 C2H6OS 1348 suppliers $15.00-$120900.00
L-Glutamine 56-85-9 C5H10N2O3 1143 suppliers $5.00-$10696.00
Glutathione 70-18-8 C10H17N3O6S 1138 suppliers $6.00-$3420.00
Sodium dodecyl sulfate 151-21-3 C12H26O4S.Na 1122 suppliers $6.00-$3140.00
D(+)-Glucose 50-99-7 C6H12O6 1119 suppliers $6.00-$26950.00
Cholesterol 57-88-5 C27H46O 925 suppliers $10.00-$67983.00
Tween 80 9005-65-6 C24H44O6 772 suppliers $25.00-$2570.00
Sodium pyruvate 113-24-6 C3H5NaO3 668 suppliers $13.00-$884.00
2-Deoxy-D-glucose 154-17-6 C6H12O5 623 suppliers $6.00-$3030.00
Phenylmethylsulfonyl fluoride 329-98-6 C7H7FO2S 413 suppliers $5.00-$2530.00

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