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

Abstract

Rui Yang,1,* Leilei Wang,2,* Zhifeng Wu,3 Yongxiang Yin,4 Shi-Wen Jiang1 1Center of Reproductive Medicine, State Key Laboratory of Reproductive Medicine, Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China; 2Department of Medical Genetics, Lianyungang Maternal and Child Health Hospital Affiliated to Yangzhou University, Lianyungang, 222000, Jiangsu, People’s Republic of China; 3Department of Ophthalmology, The Affiliated Wuxi Clinical College of Nantong University, Wuxi, 214002, Jiangsu, People’s Republic of China; 4Department of Pathology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Wen Jiang, Center of Reproductive Medicine, State Key Laboratory of Reproductive Medicine, Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: 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 inhibitors and conventional drugs, which may lead to synergistic effects. Unsolved issues impeding the research progression on O-GlcNAcylation-targeting scheme are also discussed.Graphical Abstract: Keywords: O-GlcNAcylation, nanocarriers, OGT inhibitor, targeted therapy, lectin, combined therapy

Keywords

• o-glcnacylation
• nanocarriers
• ogt inhibitor
• targeted therapy
• lectin
• combined therapy