Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy

Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy
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使用上转换纳米颗粒进行药物输送,用于多功能靶向癌细胞成像和治疗

DOI:
10.1016/j.biomaterials.2010.09.069
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发表时间:
2011-02-01
期刊:
影响因子:
14
通讯作者:
Liu, Zhuang
Liu, Zhuang
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang, Chao;Cheng, Liang;Liu, Zhuang

文献摘要

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上转换纳米粒子(UCNPs)具有独特的多光子激发光致发光特性,近年来被广泛应用于低背景生物医学成像。在这项工作中,我们官能化UCNPs与聚乙二醇(PEG)接枝的两亲性聚合物。聚乙二醇化的UCNP通过超分子化学方法通过简单的物理吸附负载有常用的化疗分子阿霉素(DOX),用于细胞内药物递送。DOX在UCNPs上的负载和释放受pH值的控制,在酸性环境中药物解离速率增加,有利于药物的控制释放。通过改进的激光扫描共聚焦显微镜进行的上转换发光(UCL)成像揭示了UCNP在细胞内递送DOX的时间过程。发现DOX通过UCNP纳米载体穿梭进入细胞,并在胞吞后在细胞内释放。通过将纳米颗粒与叶酸结合,其靶向在各种类型的癌细胞上过表达的叶酸受体,我们进一步证明了UCNP的靶向药物递送和UCL细胞成像。除了DOX之外,这种非共价药物负载策略还可以用于将光敏剂分子负载到UCNP上,用于潜在的近红外光诱导的光动力学治疗。我们的研究结果表明,UCNPs作为多功能癌症治疗和成像的有趣的纳米载体的承诺。(c)2010爱思唯尔有限公司版权所有。
Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracellular delivery of DOX by UCNPs. It is found that DOX is shuttled into cells by the UCNP nano carrier and released inside cells after endocytosis. By conjugating nanoparticles with folic acid, which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted drug delivery and UCL cell imaging with UCNPs. Besides DOX, this non-covalent drug loading strategy can also be used for loading of photosensitizer molecules on UCNPs for potential near-infrared light induced photodynamic therapy. Our results suggest the promise of UCNPs as interesting nano carriers for multi-functional cancer therapy and imaging. (c) 2010 Elsevier Ltd. All rights reserved.