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用于癌症主动靶向的逐层纳米颗粒平台。

Layer-by-layer nanoparticle platform for cancer active targeting.

作者信息

Suh Min Sung, Shen Jie, Kuhn Liisa T, Burgess Diane J

机构信息

Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.

Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.

出版信息

Int J Pharm. 2017 Jan 30;517(1-2):58-66. doi: 10.1016/j.ijpharm.2016.12.006. Epub 2016 Dec 5.

Abstract

Nanoparticles as drug delivery carriers have been investigated over the last few decades, particularly for cancer treatment. The rationale in developing such nanoparticles is to maximize drug efficacy while minimizing toxic side effects. This can be most effectively achieved through target specific drug delivery. A novel biocompatible nanoparticle platform prepared using the core-shell self-assembly technique is reported. The core consists of calcium phosphate which is biocompatible and pH-sensitive, and the shell is composed of biocompatible polymers (hyaluronic acid, CD44 targeting moiety; and chitosan, physical cross-linker). Cisplatin was selected as a model drug and incorporated between the core and the shell. The nanoparticle composition was optimized for high serum stability and low protein binding. These nanoparticles demonstrated target specific delivery in human lung cancer cells (which overexpress CD44 receptors). The targeting ability of the nanoparticles was confirmed with an 8-fold increase of drug efficacy (IC) compared to cisplatin. Furthermore, the pH-sensitive core of the nanoparticle platform led to controlled drug release through destabilization in acidic conditions. This platform technology provides a simple approach for the design of targeted biocompatible nanoparticles for cancer therapy.

摘要

在过去几十年中,纳米颗粒作为药物递送载体一直受到研究,尤其是用于癌症治疗。开发此类纳米颗粒的基本原理是在将毒副作用降至最低的同时最大化药物疗效。这可以通过靶向特异性药物递送最有效地实现。报道了一种使用核壳自组装技术制备的新型生物相容性纳米颗粒平台。核由具有生物相容性且对pH敏感的磷酸钙组成,壳由生物相容性聚合物(透明质酸,CD44靶向部分;以及壳聚糖,物理交联剂)组成。选择顺铂作为模型药物并掺入核与壳之间。对纳米颗粒组成进行了优化,以实现高血清稳定性和低蛋白结合。这些纳米颗粒在人肺癌细胞(过表达CD44受体)中表现出靶向特异性递送。与顺铂相比,纳米颗粒的靶向能力通过药物疗效(IC)提高8倍得到证实。此外,纳米颗粒平台的pH敏感核通过在酸性条件下的不稳定导致药物的可控释放。这种平台技术为设计用于癌症治疗的靶向生物相容性纳米颗粒提供了一种简单方法。

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