Nanoparticle-Mediated Delivery of 2-Deoxy-D-Glucose Induces Antitumor Immunity and Cytotoxicity in Liver Tumors in Mice.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Hepatocellular
/ chemically induced
Cell Culture Techniques
Cell Line, Tumor
Coculture Techniques
Deoxyglucose
/ administration & dosage
Drug Resistance, Neoplasm
/ drug effects
Drug Synergism
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Interferon-gamma
/ metabolism
Liver Neoplasms
/ drug therapy
Liver Neoplasms, Experimental
/ chemically induced
Male
Mice
Nanoparticle Drug Delivery System
/ chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
/ chemistry
Tumor Escape
/ drug effects
Warburg Effect, Oncologic
/ drug effects
Xenograft Model Antitumor Assays
Chemokine
IFN-γ
Lactate
PLGA
Programmed Death 1
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2021
2021
Historique:
received:
03
07
2020
revised:
18
10
2020
accepted:
19
10
2020
pubmed:
17
11
2020
medline:
21
12
2021
entrez:
16
11
2020
Statut:
ppublish
Résumé
Immune checkpoint inhibitors have shed light on the importance of antitumor immunity as a therapeutic strategy for hepatocellular carcinoma (HCC). The altered glucose metabolism known as the Warburg effect recently has gained attention as a cancer immune-resistance mechanism. Considering glycolysis inhibitors as therapeutic agents, their specific delivery to cancer cells is critical not to induce adverse effects. Thus, we investigated antitumor effects of a glycolysis inhibitor, consisting of 2-deoxy-D-glucose (2DG)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (2DG-PLGA-NPs), against hepatocellular carcinoma in mice. The antitumor effects of 2DG-PLGA-NPs were examined using hepatoma cell lines, xenograft tumors, and hepatocarcinogenic and syngeneic mouse models. The 2DG-PLGA-NPs induced cytotoxic effects and antitumor immunity through enhanced T-cell trafficking. In addition, 2DG-PLGA-NPs induced decreased lactate production and increased interferon-γ-positive T cells in liver tumors. Human CD8 The newly developed 2DG-PLGA-NPs showed antitumor immunity and cytotoxicity in liver tumors in mice, suggesting the potential of 2DG-PLGA-NPs for future clinical applications.
Sections du résumé
BACKGROUND & AIMS
Immune checkpoint inhibitors have shed light on the importance of antitumor immunity as a therapeutic strategy for hepatocellular carcinoma (HCC). The altered glucose metabolism known as the Warburg effect recently has gained attention as a cancer immune-resistance mechanism. Considering glycolysis inhibitors as therapeutic agents, their specific delivery to cancer cells is critical not to induce adverse effects. Thus, we investigated antitumor effects of a glycolysis inhibitor, consisting of 2-deoxy-D-glucose (2DG)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (2DG-PLGA-NPs), against hepatocellular carcinoma in mice.
METHODS
The antitumor effects of 2DG-PLGA-NPs were examined using hepatoma cell lines, xenograft tumors, and hepatocarcinogenic and syngeneic mouse models.
RESULTS
The 2DG-PLGA-NPs induced cytotoxic effects and antitumor immunity through enhanced T-cell trafficking. In addition, 2DG-PLGA-NPs induced decreased lactate production and increased interferon-γ-positive T cells in liver tumors. Human CD8
CONCLUSIONS
The newly developed 2DG-PLGA-NPs showed antitumor immunity and cytotoxicity in liver tumors in mice, suggesting the potential of 2DG-PLGA-NPs for future clinical applications.
Identifiants
pubmed: 33191170
pii: S2352-345X(20)30173-9
doi: 10.1016/j.jcmgh.2020.10.010
pmc: PMC7841526
pii:
doi:
Substances chimiques
IFNG protein, human
0
IFNG protein, mouse
0
Immune Checkpoint Inhibitors
0
Nanoparticle Drug Delivery System
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
Interferon-gamma
82115-62-6
Deoxyglucose
9G2MP84A8W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
739-762Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.