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

利用 MMP-2 和 MMP-9 结合配体进行脂质体肿瘤靶向药物输送

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

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.

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