Glycopolymers for Efficient Inhibition of Galectin-3: In Vitro Proof of Efficacy Using Suppression of T Lymphocyte
Apoptosis and Tumor Cell Migration
Posted on 2020-07-22 - 17:46
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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Filipová, Marcela; Bojarová, Pavla; Rodrigues Tavares, Marina; Bumba, Ladislav; Elling, Lothar; Chytil, Petr; et al. (1753). Glycopolymers for Efficient Inhibition of Galectin-3: In Vitro Proof of Efficacy Using Suppression of T Lymphocyte
Apoptosis and Tumor Cell Migration. ACS Publications. Collection. https://doi.org/10.1021/acs.biomac.0c00515