Glyco-nano-oncology: Novel therapeutic opportunities by combining small and sweet

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• 作者：Pablo F. Hockl^a ; ¹ ; Alejandro Wolosiuk^b ; ¹ ; Juan M. Pé ; rez-Sá ; ez^a ; ¹ ; Andrea V. Bordoni^b ; Diego O. Croci^a ; ^c ; Yamili Toum-Terrones^b ; Galo J.A.A. Soler-Illia^d ; ^e ; ² ; ^{galo.soler.illia@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Gabriel A. Rabinovich^a ; ^e ; ² ; ^{gabyrabi@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Glycobiology ; Nanotechnology ; Cancer ; Drug delivery ; Galectins ; Theranostics
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：109
• 期：Complete
• 页码：45-54
• 全文大小：1803 K

文摘

Recent efforts toward defining the molecular features of the tumor microenvironment have revealed dramatic changes in the expression of glycan-related genes including glycosyltransferases and glycosidases. These changes affect glycosylation of proteins and lipids not only in cancer cells themselves, but also in cancer associated-stromal, endothelial and immune cells. These glycan alterations including increased frequency of β1,6-branched N-glycans and bisecting N-glycans, overexpression of tumor-associated mucins, preferred expression of T, Tn and sialyl-Tn antigen and altered surface sialylation, may contribute to tumor progression by masking or unmasking specific ligands for endogenous lectins, including members of the C-type lectin, siglec and galectin families. Differential expression of glycans or glycan-binding proteins could be capitalized for the identification of novel biomarkers and might provide novel opportunities for therapeutic intervention. This review focuses on the biological relevance of lectin-glycan interactions in the tumor microenvironment (mainly illustrated by the immunosuppressive and pro-angiogenic activities of galectin-1) and the design of functionalized nanoparticles for pharmacological delivery of multimeric glycans, lectins or selective inhibitors of lectin-glycan interactions with antitumor activity.