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Review
. 2021 Dec;28(1):2329-2347.
doi: 10.1080/10717544.2021.1995081.

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

Xianhu Zeng  1 , Zhipeng Li  1 , Chunrong Zhu  1 , Lisa Xu  2 , Yong Sun  1 , Shangcong Han  1
Affiliations
Review

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

Xianhu Zeng et al. Drug Deliv. 2021 Dec.

Abstract

In recent years, the incidence of various types of tumors has gradually increased, and it has also been found that there is a certain correlation between abnormal glucose and lipid metabolism and tumors. Glycolipid metabolism can promote tumor progression through multiple pathways, and the expression of related genes also directly or indirectly affects tumor metabolism, metastasis, invasion, and apoptosis. There has been much research on targeted drug delivery systems designed for abnormal glucose and lipid metabolism due to their accuracy and efficiency when used for tumor therapy. In addition, gene mutations have become an important factor in tumorigenesis. For this reason, gene therapy consisting of drugs designed for certain specifically expressed genes have been transfected into target cells to express or silence the corresponding proteins. Targeted gene drug vectors that achieve their corresponding therapeutic purposes are also rapidly developing. The genes related to glucose and lipid metabolism are considered as the target, and a corresponding gene drug carrier is constructed to influence and interfere with the expression of related genes, so as to block the tumorigenesis process and inhibit tumor growth. Designing drugs that target genes related to glucose and lipid metabolism within tumors is considered to be a promising strategy for the treatment of tumor diseases. This article summarizes the chemical drugs/gene drug delivery systems and the corresponding methods used in recent years for the treatment of abnormal glucose and lipid metabolism of tumors, and provides a theoretical basis for the development of glucolipid metabolism related therapeutic methods.

Keywords: Targeted nano-drug carrier; abnormal glucose and lipid metabolism; gene carrier drugs; tumors.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
The glucose metabolism process. Glucose enters the cell via a glucose transporter (GLUT). The glycolysis process uses multiple enzymes, including HK, PFK, and PK. Gluconeogenesis affects TCA, PPP, and other processes. Three key enzymes regulate this effect in gluconeogenesis, namely, glucose-6-phosphatase-alpha (G6PC), FBP, and PEPCK. Pyruvate enters the mitochondria and generates carbon dioxide and water through the TCA pathway, which is catalyzed by three key enzymes: IDH, CS, and ketoglutarate dehydrogenase complex (KGDHC). G6PD is a key enzyme in the oxidation process of the PPP pathway, and regulates the reaction of the PPP process in the cytoplasm.
Figure 2.
Figure 2.
The lipid metabolism process. FA enters the cell through CD36. FA is catalyzed by the ACSL enzyme in the cell to generate FA-CoA, which is a precursor of acetyl-CoA and is used as a substrate in the TCA reaction in the mitochondria. The role of FA-CoA in DGAT is to generate TG and secrete lipid droplets to store energy.
Figure 3.
Figure 3.
Summary of gene vectors constructed from various materials.
Figure 4.
Figure 4.
Schematic diagram of exosomes entering targeted cells. Exosomes can enter cells through a variety of signaling pathways, and their contents include mRNA, proteins, and antigens. This figure has been adapted/reproduced from ref 135 with permission from John Wiley and Sons.
Figure 5.
Figure 5.
Schematic diagram of NPsiGLUT3 synthesis and its mechanism of action in the body. This figure has been adapted/reproduced from ref 152 with permission from ELSEVIER, Copyright 2015.
Figure 6.
Figure 6.
Schematic diagram of the construction of RGD-PEG-DSPE/DOPA/CAP nanoparticles, and mechanism of action of the RGD-PEG-DSPE/DOPA/CAP nanoparticle tumor treatment. This figure has been adapted/reproduced from ref 155 with permission from Dove Medical Press, Copyright 2019.
Figure 7.
Figure 7.
Preparation of HA-coated MDR1 siRNA/TH287-loaded MSN, and the mode of action for MDR1 siRNA/TH287-loaded MSN.
Figure 8.
Figure 8.
Schematic diagram of the preparation process of aCD3/F/AN and its mechanism of action in vivo. This figure has been adapted/reproduced from ref 161 with permission from Springer, Copyright 2021.
See this image and copyright information in PMC

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Grants and funding

This work was supported by the National Natural Science Foundation of China [81601591].