Floxuridine Homomeric Oligonucleotides “Hitchhike” with Albumin In Situ for Cancer Chemotherapy

Automated attachment of chemotherapeutic drugs to oligonucleotides through phosphoramidite chemistry and DNA synthesis has emerged as a powerful technology in constructing structure‐defined and payload‐tunable oligonucleotide–drug conjugates. In practice, however, in vivo delivery of these oligonucleotides remains a challenge. Inspired by the systemic transport of hydrophobic payloads by serum albumin in nature, we report the development of a lipid‐conjugated floxuridine homomeric oligonucleotide (LFU20) that “hitchhikes” with endogenous serum albumin for cancer chemotherapy. Upon intravenous injection, LFU20 immediately inserts into the hydrophobic cave of albumin to form an LFU20/albumin complex, which accumulates in the tumor by the enhanced permeability and retention (EPR) effect and internalizes into the lysosomes of cancer cells. After degradation, cytotoxic floxuridine monophosphate is released to inhibit cell proliferation.     

混合溶剂体系中牛肝β-半乳糖苷酶催化5-氟-2'-脱氧尿苷区域选择性半乳糖基化反应

研究了混合溶剂体系中有机溶剂种类和含量对牛肝β-半乳糖苷酶催化5-氟-2'-脱氧尿苷区域选择性半乳糖基化反应的影响.结果表明,在含10%(体积分数)有机溶剂体系中,该酶稳定性差,失活严重.减少有机溶剂含量可显著减轻其对该酶的毒害作用.然而,有机溶剂的添加对酶促糖基化反应的区域选择性的影响很小(均保持在99%以上).牛肝...     

氟尿苷-层状双金属氢氧化物纳米杂化物制备及表征

采用共沉淀法将抗癌药物氟尿苷插入Mg-Al层状双金属氢氧化物(LDHs)的层间,合成了氟尿苷-LDHs纳米杂化物。依据氟尿苷分子大小和杂化物通道高度推测,氟尿苷分子是以长轴垂直或略倾斜于LDHs层片在LDHs层间呈双层排列。分别在pH=4.8和7.2的介质中研究了药物释放动力学,表明符合准二级动力学方程;释放速率随载药量增大而降低;氟尿苷-LDHs纳米杂化物具有良好的缓释效果。