Qufu Normal University, College of Life Sciences, 57 Jingxuan West Road, Qufu City, Shandong, China.
Institution School of Food Science and Nutrition, University of Leeds, Woodhouse Ln, Leeds, LS2 9JT, UK.
ChemistryOpen. 2021 Apr;10(4):408-413. doi: 10.1002/open.202000226. Epub 2021 Feb 19.
A novel method for the preparation of antitumor drug vehicles has been optimized. Biological materials of chitosan oligosaccharide (CO) and γ-polyglutamic acid (γ-PGA) have previously been employed as modifiers to covalently modify graphene oxide (GO), which in turn loaded doxorubicin (DOX) to obtain a nano drug delivery systems of graphene oxide based composites (GO-CO-γ-PGA-DOX). The system was not equipped with the ability of initiative targeting, thus resulting into toxicity and side effects on normal tissues or organs. In order to further improve the targeting property of the system, the nucleic acid aptamer NH -AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO-CO-γ-PGA to yield the targeted nano drug delivery system APT-GO-CO-γ-PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex have been studied using multiple characterization methods. Drug loading and release profile data showed that APT-GO-CO-γ-PGA is provided with high drug loading capacity and is capable of controlled and sustained release of DOX. Cell experimental results indicated that since C23 was overexpressed on the surface of Hela cells but not on the surface of Beas-2B cells, APT-GO-CO-γ-PGA-DOX can target Hela cells and make increase toxicity to Hela cells than Beas-2B cells, and the IC value of APT-GO-CO-γ-PGA-DOX was 3.23±0.04 μg/mL. All results proved that APT-GO-CO-γ-PGA can deliver antitumor drugs in a targeted manner, and achieve the effect of reducing poison, which indicated that the targeted carrier exhibits a broad application prospect in the field of biomedicine.
一种新型的抗肿瘤药物载体的制备方法已被优化。壳聚糖寡糖 (CO) 和 γ-聚谷氨酸 (γ-PGA) 的生物材料以前曾被用作修饰物,以共价修饰氧化石墨烯 (GO),然后负载阿霉素 (DOX),从而获得基于氧化石墨烯的复合材料的纳米药物传递系统 (GO-CO-γ-PGA-DOX)。该系统不具备主动靶向能力,因此对正常组织或器官产生毒性和副作用。为了进一步提高该系统的靶向性,使用靶向核仁素 (C23) 的核酸适体 NH-AS1411 (APT) 对 GO-CO-γ-PGA 进行偶联,得到靶向纳米药物传递系统 APT-GO-CO-γ-PGA。采用多种表征方法研究了合成复合物的结构、组成、分散性、粒径和形貌特性。药物负载和释放曲线数据表明,APT-GO-CO-γ-PGA 具有高载药能力,并能够控制和持续释放 DOX。细胞实验结果表明,由于 C23 在 Hela 细胞表面过表达,而在 Beas-2B 细胞表面不表达,因此 APT-GO-CO-γ-PGA-DOX 可以靶向 Hela 细胞,并使其对 Hela 细胞的毒性增加比 Beas-2B 细胞更高,而 APT-GO-CO-γ-PGA-DOX 的 IC 值为 3.23±0.04μg/mL。所有结果都证明了 APT-GO-CO-γ-PGA 可以靶向递送抗肿瘤药物,并达到降低毒性的效果,这表明靶向载体在生物医学领域具有广阔的应用前景。