Ye Yang,Tingting Guo,Junwei Xu,Yin Xiong,Xiuming Cui,Yang Ke,Chengxiao Wang
Here, we fabricated amphiphilic polysaccharide micelles for synergistic cancer immunotherapy targeting tumor-associated macrophages (TAMs). Lepidium meyenii Walp. (maca) polysaccharide (MP), a naturally derived macromolecule with a strong TAM-remodeling effect, was grafted on a hydrophobic poly(lactic- co -glycolic acid) (PLGA) segment, with a disulfide bond for redox-sensitive linkage. The amphiphilic polysaccharide derivatives could self-assemble into core (PLGA)–shell (MP)-structured micelles and encapsulate chloroquine (CQ) into the hydrophobic core. By using a 4T1-M2 macrophage co-culture model and a 4T1 tumor xenograft mouse model, we showed that the prepared micelles could co-deliver MP and CQ to the tumor sites and selectively accumulate at TAMs because of the specific properties of MP. Furthermore, the nanoparticles exerted synergistic tumor immunotherapeutic and antimetastatic effects, which might be attributable to the enhanced cell internalization of the micelles and the multiple regulatory mechanisms of MP and CQ. Thus, immunomodulatory MP may be a promising biomaterial for cancer immunotherapy.
en This link goes to a English section pt This link goes to a English section Maca ( Lepidium meyenii Walp) polysaccharides (MP) with purity of 99.2% were obtained to investigate their structural characteristics and antifatigue effect in vivo . The physicochemical properties of MP were analyzed through high-performance gel filtration chromatography, IR, monosaccharide composition, methylation, GC-MS, and NMR analyses. The antifatigue effect of MP was evaluated by using a mouse weight-loaded swimming model. MP is an acidic heteropolysaccharide with an average molecular weight ( M w ) of 793.5 kDa. It is composed of D-GalA: D-Glc: L-Ara: D-Man: D-Gal: L-Rha = 35.07:29.98:16.98:13.01:4.21:0.75 (mol, %). The findings revealed that MP contained β-1,3-Gal p (A), β-1,3-Glc p , and α-1, 3-Man p linked alternatingly to form a backbone (5:4:1). MP (above mid-dosage 50 mg/kg bw/d) could effectively elongate swimming durations and accelerate average swimming speeds (within the 1st 5 min) of mice ( P < 0.05) and improve the serous biochemical parameters of mice. Compared with the control model, high-dosage (100 mg/kg bw/d) MP treatment could significantly enhance glutathione peroxidase and creatine kinase activities ( P < 0.05) and decreased lactate dehydrogenase activity ( P < 0.01). High-dosage MP could significantly reduce the levels of blood urea nitrogen, lactic acid, and malondialdehyde ( P < 0.05). MP is an acidic polysaccharide with a high D-GalA content, which could be responsible for the antifatigue effect of maca. Practical Application en This link goes to a English section pt This link goes to a English section The antifatigue activity of polysaccharides isolated from maca ( Lepidium meyenii Walp) was investigated in this study. Polysaccharides, as a major component of maca (above 10% in dry weight), could be explored as a natural antifatigue functional food in the future.
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