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一种有效的聚合物纳米载体,可在细胞共培养系统中实现主动靶向和选择性药物传递。

An effective polymeric nanocarrier that allows for active targeting and selective drug delivery in cell coculture systems.

机构信息

GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.

Nanogetic S.L. Avda de la Innovacion 1, PTS, Edificio BIC, 18016 - Granada, Spain.

出版信息

Nanoscale. 2021 Feb 18;13(6):3500-3511. doi: 10.1039/d0nr07145e.

DOI:10.1039/d0nr07145e
PMID:33560282
Abstract

In this manuscript, we report the development of a versatile, robust, and stable targeting nanocarrier for active delivery. This nanocarrier is based on bifunctionalized polymeric nanoparticles conjugated to a monoclonal antibody that allows for active targeting of either (i) a fluorophore for tracking or (ii) a drug for monitoring specific cell responses. This nanodevice can efficiently discriminate between cells in coculture based on the expression levels of cell surface receptors. As a proof of concept, we have demonstrated efficient delivery using a broadly established cell surface receptor as the target, the epidermal growth factor receptor (EGFR), which is overexpressed in several types of cancers. Additionally, a second validation of this nanodevice was successfully carried out using another cell surface receptor as the target, the cluster of differentiation 147 (CD147). Our results suggest that this versatile nanocarrier can be expanded to other cell receptors and bioactive cargoes, offering remarkable discrimination efficiency between cells with different expression levels of a specific marker. This work supports the ability of nanoplatforms to boost and improve the progress towards personalized medicine.

摘要

在本手稿中,我们报告了一种多功能、稳健且稳定的靶向纳米载体的开发,用于主动递药。这种纳米载体基于双功能化的聚合物纳米颗粒,与单克隆抗体连接,允许主动靶向(i)荧光团进行跟踪,或(ii)药物以监测特定的细胞反应。这种纳米器件可以根据细胞表面受体的表达水平,有效地区分共培养中的细胞。作为概念验证,我们已经证明了使用广泛建立的细胞表面受体作为靶标,即表皮生长因子受体(EGFR),在几种类型的癌症中过表达,进行有效的递药。此外,使用另一个细胞表面受体作为靶标,即分化簇 147(CD147),成功地对这种纳米器件进行了第二次验证。我们的结果表明,这种多功能纳米载体可以扩展到其他细胞受体和生物活性货物,在具有特定标志物不同表达水平的细胞之间提供显著的区分效率。这项工作支持了纳米平台能够增强和改善个性化医疗的进展。

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