How Nanotechniques Could Vitalize the O-GlcNAcylation-Targeting Approach for Cancer Therapy

作者：Rui Yang, Leilei Wang, Zhifeng Wu, Yongxiang Yin, Shi‐Wen Jiang · 发表于：International Journal of Nanomedicine · 年份：2022 · DOI：10.2147/ijn.s360488 · 被引用次数：11 · 研究领域：Glycosylation and Glycoproteins Research、Galectins and Cancer Biology、Carbohydrate Chemistry and Synthesis

Accumulated data indicated that many types of cancers have increased protein O-GlcNAcylation at cell surface and inside cells. The aberrant O-GlcNAcylation is considered a potential therapeutic target. Although several types of compounds capable of inhibiting O-GlcNAcylation have been developed, their low solubility, poor permeability and delivery efficiency have impeded the application for in vivo and pre-clinical studies. Nanocarriers have the advantages of controllable drug release and active cancer-targeting capability. Moreover, nanoparticles can improve drug delivery efficiency and reduce the non-specific distribution in normal tissues by the enhanced permeability and retention (EPR) effect in cancer. Taking the advantage of O-GlcNAc-specific antibodies or lectins, nanoparticles could further improve their cancer-targeting capability. Although nanocarriers targeting the canonical N- and O-linked glycosylation have been extensively investigated for cancer detection and therapy, application of nanotechniques for the specific targeting of O-GlcNAcylation has not been actively pursued. This review summarizes the general features of GlcNAcylation and its alterations in cancers. Analyses are focused on the following areas: How the nanocarriers may improve the solubility and/or cell permeability of O-GlcNAc transferase (OGT) inhibitors; The modification of nanocarriers with lectins or antibodies for active targeting of O-GlcNAc; The nanocarriers-mediated co-delivery of OGT inh...