Hyaluronic acid carrier-cell interactions: a tri-culture model of the tumour microenvironment to study siRNA delivery under flow conditions

Q4 Chemistry

International Journal of Nano and Biomaterials Pub Date : 2019-08-19 DOI:10.1504/IJNBM.2019.10023325

J. Rosa, N. Tirelli, A. Tirella

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引用次数: 0

Abstract

CD44 is often over expressed in solid tumours, rendering this protein a 'hot' target in drug delivery. As CD44 is the main surface receptor of hyaluronic acid (HA), one of the most common therapeutic approaches consists of hijacking the cell's mechanism of HA endocytosis to deliver active principles. This approach, however, presents two caveats: the poor understanding of HA-cell interactions and the ubiquitous expression of CD44 in other cell types, e.g., stromal cells. To predict the interaction of HA-decorated nanocarriers with CD44-expressing cells in the multi-cellular and complex tumour microenvironment, we have established a tri-culture, non-contact in vitro model (PANC-1 tumoural cells, HDF stromal cells, THP-1 macrophages) and quantified the delivery and kinetics of nanoparticle internalisation (via flow cytometry), investigating the system in both static and dynamic culturing conditions. We report that HA-decorated nanocarriers are able to preferentially deliver siRNA to pancreatic cancer cells, interestingly even under flow/dynamic conditions.

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透明质酸载体-细胞相互作用：肿瘤微环境的三种培养模型，用于研究流动条件下siRNA的递送

CD44在实体瘤中经常过度表达，使这种蛋白质成为药物递送中的“热门”靶点。由于CD44是透明质酸（HA）的主要表面受体，最常见的治疗方法之一是劫持细胞的HA内吞机制以提供活性成分。然而，这种方法提出了两个警告：对HA细胞相互作用的了解不足，以及CD44在其他细胞类型（如基质细胞）中普遍表达。为了预测HA修饰的纳米载体与CD44表达细胞在多细胞和复杂肿瘤微环境中的相互作用，我们建立了一个三培养、非接触的体外模型（PANC-1肿瘤细胞、HDF基质细胞、THP-1巨噬细胞），并量化了纳米颗粒内化的递送和动力学（通过流式细胞术），在静态和动态培养条件下研究该系统。我们报道，即使在流动/动态条件下，HA修饰的纳米载体也能够优先将siRNA递送到胰腺癌症细胞。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Nano and Biomaterials Chemistry-Physical and Theoretical Chemistry

CiteScore

1.20

自引率

0.00%

发文量

期刊介绍： In recent years, frontiers of research in engineering, science and technology have been driven by developments in nanomaterials, encompassing a diverse range of disciplines such as materials science, biomedical engineering, nanomedicine and biology, manufacturing technology, biotechnology, nanotechnology, and nanoelectronics. IJNBM provides an interdisciplinary vehicle covering these fields. Advanced materials inspired by biological systems and processes are likely to influence the development of novel technologies for a wide variety of applications from vaccines to artificial tissues and organs to quantum computers. Topics covered include Nanostructured materials/surfaces/interfaces Synthesis of nanostructures Biological/biomedical materials Artificial organs/tissues Tissue engineering Bioengineering materials Medical devices Functional/structural nanomaterials Carbon-based materials Nanomaterials characterisation Novel applications of nanomaterials Modelling of behaviour of nanomaterials Nanomaterials for biomedical applications Biological response to nanomaterials.