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A cis-Diol/pH Dual-Responsive Upconversion Nanoplatform: Synthesis, Characterization, and In Vitro Demonstration.
Journal of Biomedical Nanotechnology Pub Date : 2019-6-6 , DOI: 10.1166/jbn.2019.2700
Hui Cui , Bowen Zhang , Haolin Ding , Youming Hu , Xianhua Wang , Liang Xu , Xiaojie Jiao , Huining He , Xu Wang , Xianshun Zeng , Victor C. Yang

Integrating the functions of bioimaging, targeting and controlled release of therapeutic agents into a single nanoparticle is of great interests in nanomedicine and nanobiology. Herein, a cis -diol/pH dual-responsive upconversion nanoparticle (UCNP)-based theranostic platform has been developed for delivery of the anticancer drug to cancer cells. This nanoplatform is based on the strategic design of targetable hyaluronan modified UCNPs (HA-UCNPs) that are coupled with aminobenzeneboronic acid (APBA) to obtain APBA-UCNPs, having favorable tumor selectivity as well as the capacity for capturing cis-diol-containing therapeutics. The controlled release function is then achieved through the self-assembly of hydroxycamptothecin derivative ligands onto the surfaces of APBA-UCNPs, which is controllable in a stimuli-dependent manner. The UCNP-based theranostic probe taken up by tumor cells via receptor-mediated endocytosis liberates drugs triggered by competitive glucose at low pH in endosomes/lysosomes, resulting in cell apoptosis. The dual-responsive mechanism of boronate ester bonds gives a chemoselective strategy for controlled release of drug within tumor cells, establishing an alternative approach to treat a broad spectrum of diseases exploiting similar boronic acid-involved therapeutics.

中文翻译:

顺式二元醇/ pH双响应上转换纳米平台:合成,表征和体外演示。

在纳米医学和纳米生物学中,将生物成像功能,靶向治疗药物和控制药物的控制释放整合到单个纳米颗粒中非常重要。本文中,已经开发了基于顺式-二醇/ pH双响应上转换纳米颗粒(UCNP)的治疗学平台,用于将抗癌药递送至癌细胞。该纳米平台基于可靶向的透明质酸修饰的UCNP(HA-UCNP)与氨基苯硼酸(APBA)偶联以获得APBA-UCNP的战略设计,具有良好的肿瘤选择性以及捕获顺式的能力-含二醇的治疗剂。然后,通过将羟基喜树碱衍生物配体自组装到APBA-UCNPs的表面上来实现控释功能,这可以以刺激依赖性方式来控制。肿瘤细胞通过受体介导的内吞作用吸收的基于UCNP的治疗试剂可释放内体/溶酶体中低pH竞争葡萄糖触发的药物,从而导致细胞凋亡。硼酸酯键的双重反应机制为肿瘤细胞内药物的受控释放提供了化学选择性策略,从而建立了一种利用广泛的涉及硼酸的疗法来治疗多种疾病的替代方法。
更新日期:2020-08-21
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