A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites.

A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites.
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DOI:
10.1002/open.202000226
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发表时间:
2021-04
期刊:
影响因子:
2.3
通讯作者:
Yang G
Yang G
中科院分区:
化学3区
文献类型:
--
作者:
Liu B;Yang W;Che C;Liu J;Si M;Gong Z;Gao R;Yang G

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优化了一种制备抗肿瘤药物载体的新方法。壳聚糖低聚糖(CO)和γ‐聚谷氨酸(γ‐PGA)的生物材料先前已被用作共价修饰氧化石墨烯(GO)的改性剂,氧化石墨烯又负载阿霉素(DOX),以获得氧化石墨烯基复合材料(GO‐CO‐γ‐PGA‐DOX)的纳米药物递送系统。该系统不具备主动靶向的能力,对正常组织或器官有毒副作用。为了进一步提高体系的靶向性,将靶向核蛋白(C23)的核酸适体NH2‐AS1411 (APT)偶联在GO‐CO‐γ‐PGA上,得到靶向纳米给药体系APT‐GO‐CO‐γ‐PGA。采用多种表征方法对合成的配合物的结构、组成、分散、粒度和形貌进行了研究。载释谱数据表明,APT - GO - CO - γ - PGA具有较高的载药能力,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细胞表面未过表达,APT‐GO‐CO‐γ‐PGA‐DOX可靶向Hela细胞,对Hela细胞的毒性比Beas‐2B细胞大,其IC50值为3.23±0.04 μg/mL。这些结果都证明了APT‐GO‐CO‐γ‐PGA能够靶向传递抗肿瘤药物,并达到减毒的效果,这表明靶向载体在生物医学领域具有广阔的应用前景。已经报道了一种能够提高主动靶向和治疗效果的纳米药物递送系统。利用靶向核蛋白(C23)的核酸适体NH2‐AS1411 (APT)偶联GO‐CO‐γ‐PGA,得到靶向纳米给药体系APT‐GO‐CO‐γ‐PGA。通过多种表征方法对合成的配合物的结构、组成、分散、粒径和形态特性进行分析,发现其具有较高的载药能力、药物的控释和缓释能力以及靶向Hela细胞的能力。
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 NH2‐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 IC50 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. A nano drug delivery system able to enhance active targeting and therapeutic efficacy has been reported. Nucleic acid aptamer NH2‐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 were analyzed via multiple characterization methods to find high drug loading capacity, the ability of controlled and sustained release of drugs, and the targeting to Hela cells.
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