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基于葡聚糖封端树枝状介孔硅纳米粒子的杂化纳米储库用于 CD133 靶向药物传递。

Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery.

机构信息

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Cell Physiol. 2020 Feb;235(2):1036-1050. doi: 10.1002/jcp.29019. Epub 2019 Jul 5.

Abstract

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.

摘要

在这项研究中,树枝状介孔硅纳米粒子(DMSNs)的化学特性为设计一种具有智能将有效载荷输送到肿瘤细胞的能力的纳米结构提供了机会。在这方面,阿霉素(DOX)包封的 DMSNs 被静电表面涂覆以聚羧酸葡聚糖(PCAD),以提供具有控制 pH 值依赖性药物释放的生物相容性葡聚糖封端的 DMSNs(PCAD-DMSN@DOX)。此外,针对癌症干细胞(CSC)标志物 CD133 的 RNA 适体被共价连接到 DEX 的羧基上,以产生 CD133-PCAD-DMSN@DOX。然后,利用所制备的纳米系统将 DOX 有效地递送到 CD133+结直肠癌细胞(HT29)。细胞摄取和细胞毒性的体外评估表明,CD133-PCAD-DMSN@DOX 特异性地靶向 HT29,这是通过流式细胞术和 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐测定证实的 CD133 过表达癌细胞。该具有潜力的智能靶向平台表明,靶向葡聚糖封端的 DMSNs 可能在癌症治疗中具有令人印象深刻的应用。

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