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利用基质金属蛋白酶-2和基质金属蛋白酶-9结合配体的脂质体肿瘤靶向给药

Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands.

作者信息

Penate Medina Oula, Haikola Merja, Tahtinen Marja, Simpura Ilkka, Kaukinen Sami, Valtanen Heli, Zhu Ying, Kuosmanen Sari, Cao Wei, Reunanen Justus, Nurminen Tuula, Saris Per E J, Smith-Jones Peter, Bradbury Michelle, Larson Steven, Kairemo Kalevi

机构信息

Department of Radiology, Sloan Kettering Institute for Cancer Research, 1275 York Ave., New York, NY 10065, USA.

出版信息

J Drug Deliv. 2011;2011:160515. doi: 10.1155/2011/160515. Epub 2010 Dec 29.

Abstract

Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

摘要

纳米技术通过实现不同的药物递送和控释策略,为传统治疗方案提供了一种替代方法。脂质体具有良好的生物可降解性,并且在大多数情况下基本无毒,为几种不同的递送方法提供了一个通用平台,这些方法有可能增强治疗对肿瘤的递送和靶向性。由于肿瘤内有窗孔的血管,脂质体可自发穿透肿瘤,从而产生已知的增强通透性和随后的药物滞留效应。此外,脂质体可用于携带放射性部分,如放射性示踪剂,其可在脂质体内的多个位置结合,使其成为分子成像应用的有吸引力的载体。噬菌体展示是一种可将各种高亲和力和选择性的肽递送至不同靶点的技术。在本研究中,通过噬菌体展示发现的明胶酶结合肽通过共价肽-聚乙二醇-磷脂酰乙醇胺锚定连接到脂质体上,从而创建了一种靶向药物递送载体。明胶酶作为肿瘤靶向的细胞外靶点,为肿瘤靶向提供了一种可行的替代方法。我们的研究结果表明,靶向药物递送比非靶向药物递送更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2acd/3066593/c5c961427f2e/JDD2011-160515.001.jpg

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