Department of Analytical Chemistry, School of Pharmacy , Istanbul Medipol University , İstanbul 34810 , Turkey.
Biomacromolecules. 2019 Aug 12;20(8):2962-2972. doi: 10.1021/acs.biomac.9b00528. Epub 2019 Jul 31.
An important requirement to decrease the side effects of chemotherapy drugs is to develop nanocarriers with precise biological functions. In this work, a set of glyconanoparticles was prepared via self-assembly of amphiphilic glycoblock copolymers for the targeted delivery of a hydrophobic chemotherapy drug. Well-defined glycoblock copolymers that consist of 1,1-di--butyl 3-(2-(metyloyloxy)ethyl)-butane-1,1,3-tricarboxylate (MAETC) together with three different protected-sugar moieties (β-d-glucopyranoside, β-d-mannopyranoside, and β-l-fucopyranoside) were synthesized by using reversible addition-fragmentation chain-transfer polymerization. Copolymers were deprotected and conjugated with the -dichlorodiammineplatinum(II) (-Pt) anticancer drug. Dynamic light scattering and transmission electron microscopy measurements revealed that -Pt-conjugated glyconanoparticles were sufficiently stable under physiological conditions and had diameters of approximately 100 nm with considerably narrow size distributions. They were intracellularly taken up by the breast cancer (MCF-7 and MDA-MB-231), prostate cancer (PC3), renal cancer (769-P), and Chinese hamster ovary cell lines. The PC3 and 769-P cell lines showed a high preference for the glycosylated nanoparticles. Glycoblock copolymers were found nontoxic but showed high cytotoxicity and increased efficacy after conjugation with the -Pt anticancer drug. Moreover, in vitro cytotoxicity assays in cancer cell lines demonstrate that -Pt-loaded glycopolymer-based nanoparticles have higher cytotoxicity than free -Pt. Overall, our results suggest that glyconanoparticles have a great potential to be used as an effective -Pt drug carrier for targeted cancer therapy.
降低化疗药物副作用的一个重要要求是开发具有精确生物学功能的纳米载体。在这项工作中，通过两亲性糖嵌段共聚物的自组装制备了一组糖纳米粒子，用于靶向递送疏水性化疗药物。通过可逆加成-断裂链转移聚合合成了由 1,1-二-正丁基 3-(2-(甲酰氧基)乙基)-1,1,3-丁烷三羧酸酯(MAETC)与三种不同保护糖部分(β-d-吡喃葡萄糖苷、β-d-吡喃甘露糖苷和β-l-岩藻吡喃糖苷)组成的具有明确结构的糖嵌段共聚物。共聚物脱保护并与-dichlorodiammineplatinum(II)(-Pt)抗癌药物缀合。动态光散射和透射电子显微镜测量结果表明，-Pt 缀合的糖纳米粒子在生理条件下足够稳定，直径约为 100nm，具有相当窄的粒径分布。它们被乳腺癌(MCF-7 和 MDA-MB-231)、前列腺癌(PC3)、肾癌(769-P)和中国仓鼠卵巢细胞系内化。PC3 和 769-P 细胞系对糖基化纳米粒子表现出很高的偏好。糖嵌段共聚物被发现无毒，但与 -Pt 抗癌药物缀合后显示出高细胞毒性和增强的疗效。此外，在癌细胞系中的体外细胞毒性测定表明，负载 -Pt 的糖聚合物基纳米粒子比游离 -Pt 具有更高的细胞毒性。总的来说，我们的结果表明，糖纳米粒子具有作为靶向癌症治疗的有效 -Pt 药物载体的巨大潜力。
