糖类聚合物
化学
细胞凋亡
癌症研究
细胞内
体外
生物化学
生物
共聚物
有机化学
聚合物
作者
Marcela Filipová,Pavla Bojarová,Marina Rodrigues Tavares,Ladislav Bumba,Lothar Elling,Petr Chytil,Kristýna Gunár,Vladimı́r Křen,Tomáš Etrych,Olga Janoušková
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2020-07-22
卷期号:21 (8): 3122-3133
被引量:25
标识
DOI:10.1021/acs.biomac.0c00515
摘要
The development of efficient galectin-3 (Gal-3) inhibitors draws attention in the field of anti-cancer therapy, especially due to the prominent role of extra- and intracellular Gal-3 in vital processes of cancerogenesis, such as immunosuppression, stimulation of tumor cells proliferation, survival, invasion, apoptotic resistance, and metastasis formation and progression. Here, by combining poly-LacNAc (Galβ4GlcNAc)-derived oligosaccharides with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, we synthesized multivalent glycopolymer inhibitors with a high potential to target extracellular and intracellular Gal-3. The inhibitory capabilities of the best conjugate in the studied series were in the nanomolar range proving the excellent Gal-3 inhibitory potential. Moreover, thorough investigation of the inhibitory effect in the biological conditions showed that the glycopolymers strongly inhibited Gal-3-induced apoptosis of T lymphocytes and suppressed migration and spreading of colorectal, breast, melanoma, and prostate cancer cells. In sum, the strong inhibitory activity toward Gal-3, combined with favorable pharmacokinetics of HPMA copolymers ensuring enhanced tumor accumulation via the enhanced permeability and retention effect, nominate the glycopolymers containing LacdiNAc-LacNAc (GalNAcβ4GlcNAcβ3Galβ4GlcNAc) tetrasaccharide as promising tools for preclinical in anti-cancer therapy evaluation.
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