Journal
BIOMATERIALS
Volume 284, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121523
Keywords
Glycopeptide; PKM2; Nano-activator; Glycolysis; Switching catabolic pathways
Funding
- National Natural Science Foundation of China [81771898]
- Key Research Program of Frontier Sciences, CAS [ZDBS-LY-SLH039]
- Regional Key Project of National Natural Sci-ence Foundation of China [U20A20385]
Ask authors/readers for more resources
In this study, a glycopeptide-based PKM2 nanoactivator was developed to activate PKM2 from dimers to tetramers, leading to the inhibition of tumor cell metabolism and proliferation. The nanoactivator formed nanofibrillar structures in vivo and accumulated at the tumor sites, enhancing the sensitivity to chemotherapy drugs.
Tumor cells intensively engage in metabolic reprogramming for enhancing the availability of glycolytic metabolites and support cell proliferation. As the most important rate-limiting enzyme in aerobic glycolysis, activating the pyruvate kinase muscle isoform 2 (PKM2) from dimers to tetramers has become a key tumor chemotherapy method to control glucose metabolism. Herein, we developed a glycopeptide-based PKM2 nanoactivator, which could induce the tetramerization of PKM2 based on serine bonding to Domain C of PKM2. The bound and trapped PKM2 tetramers significantly hindered glycolytic intermediates, prevented the nucleus translocation of dimeric PKM2, and ultimately inhibited the proliferation, chemoresistance and metastasis of tumor. The glycopeptide assembled into nanoparticles under aqueous conditions and in the circulation, which in situ transformed into PKM2 nano-activator with nanofibrillar structure after specifically activated by O-GlcNAcase recognition upregulated in a wide range of human tumors. Moreover, the glycopeptide-based PKM2 nanoactivator successfully accumulated at the tumor sites and boosted the chemo-drug sensitivity against prostate and breast cancers. Attributed to these intriguing results, the newly developed glycopeptide-based PKM2 nanoactivator can be envisioned a promising candidate for the treatment of tumors by switching catabolic pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available