Lactosylated Glycogen Nanoparticles for Targeting Prostate Cancer Cells
Lactosylated Glycogen Nanoparticles for Targeting Prostate Cancer Cells
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DOI：
10.1021/acsami.7b02676
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发表时间：
2017-05-24
影响因子：
9.5
通讯作者：
Cayalieri, Francesca
中科院分区：
文献类型：
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作者：
Besford, Quinn A.;Wojnilowicz, Marcin;Cayalieri, Francesca
与凝集素表现出多价结合的甘聚糖颗粒是分子识别和治疗应用的理想选择。在这里，我们探索使用糖原纳米颗粒作为工程多价糖纳米颗粒的生物源糖支架。糖原纳米颗粒是一种天然存在的葡萄糖高支化聚合物，通过铜(I)催化的炔叠氮化环加成化学，与乳糖功能化，用于与凝集素非原位和前列腺癌细胞的靶向相互作用。通过光波导光模光谱、动态光散射和石英晶体微天平测量，发现含有末端β -半乳糖苷部分的乳糖化糖原被称为半乳糖糖原（GG），并与花生凝集素（PNA）（一种β -半乳糖苷特异性凝集素）有强烈的相互作用。GG纳米颗粒与PNA的亲和力常数为3.4 x 10(5) M-1， GG - PNA复合物不能被乳糖取代，表明GG与凝集素的竞争性结合。这些GG纳米颗粒在体外测试了与前列腺癌细胞膜的关系，通过流式细胞术和共聚焦显微镜观察到，这些颗粒对细胞膜表现出高亲和力。据推测，这是由于特异性的细胞外半凝集素-1靶向所致。此外，GG纳米颗粒诱导前列腺癌细胞之间的聚集。我们的研究结果强调了一种设计生物源多糖的策略，其表面部分与凝集素表现出强烈的多价相互作用，并与前列腺癌细胞靶向相互作用。
Glyconanoparticles that exhibit multivalent binding to lectins are desirable for molecular recognition and therapeutic applications. Herein we explore the use of glycogen nanoparticles as a biosourced glycoscaffold for engineering multivalent glyconanoparticles. Glycogen nano particles, a naturally occurring highly branched polymer of glucose, was functionalized with lactose, achieved through copper(I)-catalyzed alkyne-azide cycloaddition chemistry, for targeted interaction with lectins ex situ and on prostate cancer cells. The lactosylated glycogen, which contains terminal beta-galactoside moieties, is termed galacto-glycogen (GG), and is found to interact strongly with peanut agglutinin (PNA), a beta-galactoside specific lectin, as observed by optical waveguide lightmode spectroscopy, dynamic light scattering, and quartz crystal microbalance measurements. The GG nanoparticles exhibit multivalent binding to PNA with an affinity constant of 3.4 x 10(5) M-1 and the GG PNA complex cannot he displaced by lactose, demonstrating the competitive binding of GG to the lectin. These GG nanoparticles were tested for association with prostate cancer cell membranes in vitro, where the particles exhibited a high affinity for the membrane, as observed from flow cytometry and confocal microscopy. This is inferred to result from specific extracellular galectin-1 targeting. Furthermore, the GG nanoparticles induce aggregation between prostate cancer cells. Our results highlight a strategy for engineering a biosourced polysaccharide with surface moieties that exhibit strong multivalent interactions with lectins, and targeted interaction with prostate cancer cells.