Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

Small, vol. 19, pp. e2208042

Abstract

Fasting has many health benefits, including reduced chemotherapy toxicity and improved efficacy. It is unclear how fasting affects the tumor microenvironment (TME) and tumor-targeted drug delivery. Here the effects of intermittent (IF) and short-term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are inoculated either subcutaneously or intrahepatically with Hep-55.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is found to be increased, while systemic side effects are reduced. Altogether, these findings exemplify that the beneficial effects of fasting on anticancer therapy outcomes go beyond modulating metabolism at the molecular level.

Authors 13

1. Svea Becker Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

2. Jeffrey Momoh Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

3. Ilaria Biancacci Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

4. Diana Möckel Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

5. Qingbi Wang Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

6. Jan‐Niklas May Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

   Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

7. Huan Su Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

8. Lena Susanna Candels Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

9. Marie‐Luise Berres Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

   Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

10. Fabian M. Kiessling Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

    Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

11. Maximilian Hatting Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

    Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

12. Twan Lammers corresponding Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

    Institute for Experimental Molecular Imaging (ExMI) University Hospital RWTH Aachen 52074 Aachen Germany

13. Christian Trautwein corresponding Aachen Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany

    Clinic for Gastroenterology, Metabolic Disorders, and Internal Intensive Medicine (Med III) University Hospital RWTH Aachen 52074 Aachen Germany