Zhu Qiwen, Bao Bin, Zhang Qiumeng, Yu Jiahui, Lu Wei
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University 3663 North Zhongshan Road Shanghai 200062 P. R. China
RSC Adv. 2018 Jan 12;8(5):2818-2823. doi: 10.1039/c7ra12954h. eCollection 2018 Jan 9.
Camptothecin analogs, as commonly used chemotherapy drugs, usually have poor water solubility which has limited their use in the clinic. In order to improve the water-solubility of camptothecin, a new dextran derivative Dex-Mal was synthesized and used in designing a dextran-camptothecin conjugate which contained a CTB-sensitive linker. This conjugate could efficiently release the therapeutic drug SN-38 in the presence of cathepsin B and the antiproliferative activity of the conjugate was similar to the approved drug Irinotecan hydrochloride. Furthermore, in the presence of dextran, the conjugate could self-assemble into nanoparticles in water, which could improve the targeting ability through the EPR effect. This provides a potential way to formulate a drug delivery system for camptothecin analogs or other drugs which have poor water solubility.
喜树碱类似物作为常用的化疗药物，通常水溶性较差，这限制了它们在临床上的应用。为了提高喜树碱的水溶性，合成了一种新的葡聚糖衍生物Dex-Mal，并用于设计一种含有CTB敏感连接子的葡聚糖-喜树碱缀合物。该缀合物在组织蛋白酶B存在的情况下能够有效释放治疗药物SN-38，且其抗增殖活性与已获批药物盐酸伊立替康相似。此外，在葡聚糖存在的情况下，该缀合物能够在水中自组装成纳米颗粒，通过增强渗透滞留（EPR）效应提高靶向能力。这为喜树碱类似物或其他水溶性差的药物构建药物递送系统提供了一种潜在途径。
