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叶酸修饰的光致发光二醛羧甲基纤维素交联生物纳米凝胶用于 pH 控制和肿瘤靶向共载药。

Folic acid-modified photoluminescent dialdehyde carboxymethyl cellulose crosslinked bionanogels for pH-controlled and tumor-targeted co-drug delivery.

机构信息

Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.

Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.; Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Science, Tabriz, Iran.

出版信息

Int J Biol Macromol. 2022 Mar 1;200:247-262. doi: 10.1016/j.ijbiomac.2022.01.002. Epub 2022 Jan 7.

Abstract

This work aimed to fabricate a new photoluminescent bionanogel with both targeted anticancer drug delivery and bioimaging potentials. Briefly, at first photoluminescent carbon dots (CDs) were synthesized from the low-cost and more available black pepper with traditional medicinal properties. The as-synthesized dialdehyde carboxymethyl cellulose (DCMC) was used as a safe crosslinker for gelatin crosslinking in the presence of CDs (CDs/DCMC-Gel). Eventually, the residual amine functional groups of gelatin were used for the conjugation of CDs/DCMC-Gel with folic acid (FA) ((CDs/DCMC-Gel)-FA bionanogels). All employed physicochemical characterization methods approved the (CDs/DCMC-Gel)-FA bionanogels fabrication route. SEM analysis specified the spherical morphology with a diameter of ~70-90 nm for it. Curcumin (CUR) and doxorubicin (DOX) respectively were loaded with drug entrapment efficiency of about 44.0% and 41.4%. The release rate for both drugs in acidic conditions was higher than in physiological conditions. In vitro antitumor experiments; MTT, DAPI staining, cellular uptake, and cell cycle tests showed the superior anticancer effect of the CUR@DOX@(CDs/DCMC-Gel)-FA in comparison with free CUR@DOX. Moreover, the (CDs/DCMC-Gel)-FA acted as a hopeful bio-imaging tool. Taken together, the designed (CDs/DCMC-Gel)-FA could be proposed as a promising nanosystem for efficient chemotherapy.

摘要

本工作旨在制备一种具有靶向抗癌药物递送和生物成像潜力的新型光致发光生物纳米凝胶。简而言之,首先从具有传统药用特性的廉价且更易得的黑胡椒中合成出光致发光碳点(CDs)。所合成的二醛羧甲基纤维素(DCMC)在 CDs 的存在下用作明胶交联的安全交联剂(CDs/DCMC-Gel)。最终,明胶中残留的胺官能团用于将 CDs/DCMC-Gel 与叶酸(FA)缀合((CDs/DCMC-Gel)-FA 生物纳米凝胶)。所有使用的物理化学特性分析方法都证实了(CDs/DCMC-Gel)-FA 生物纳米凝胶的制备路线。SEM 分析指定其具有约 70-90nm 的球形形貌。姜黄素(CUR)和阿霉素(DOX)的载药包封效率分别约为 44.0%和 41.4%。两种药物在酸性条件下的释放率均高于生理条件下的释放率。体外抗肿瘤实验;MTT、DAPI 染色、细胞摄取和细胞周期试验表明,CUR@DOX@(CDs/DCMC-Gel)-FA 与游离 CUR@DOX 相比具有更好的抗癌效果。此外,(CDs/DCMC-Gel)-FA 可作为有希望的生物成像工具。综上所述,所设计的(CDs/DCMC-Gel)-FA 可以作为一种用于有效化学疗法的有前途的纳米系统。

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