Targeting of polymeric nanoparticles to lung metastases by surface-attachment of YIGSR peptide from laminin

• Published in: Biomaterials Vol. 32; no. 1; pp. 152 - 161
• Main Authors: Sarfati, Gadi, Dvir, Tal, Elkabets, Moshe, Apte, Ron N, Cohen, Smadar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-2011
• Subjects: Advanced Basic Science; Animals; assays; cell culture; chemotherapy; Dentistry; Disease Models, Animal; Drug Delivery Systems - methods; drugs; fluorescent labeling; gene expression regulation; heart; in vitro studies; Injections, Intravenous; intravenous injection; Laminin; Laminin - chemistry; liver; lung neoplasms; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; lungs; melanoma; Melanoma, Experimental; Metastasis; Mice; Mice, Inbred C57BL; Microfluidics; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - therapeutic use; Oligopeptides - administration & dosage; Oligopeptides - pharmacokinetics; Oligopeptides - pharmacology; Oligopeptides - therapeutic use; peptides; polymers; Polymers - administration & dosage; receptors; Rheology - drug effects; Spectroscopy, Fourier Transform Infrared; Static Electricity; Targeting; Tissue Distribution - drug effects; Nanoparticles; Laminin; Metastasis; Targeting
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.09.014

Abstract Effective therapy for disseminated metastatic cancer is currently impossible because of low drug accumulation in target sites. Here, we aimed to enhance nanoparticle (NP) targeting to lung melanoma metastases via interactions with the laminin receptor, whose expression is upregulated in metastatic cells. To enable NP follow-up and a framework for targeting ligand binding, Estapor® fluorescent NPs (299 ± 6 nm in diameter) with surface carboxylic groups were employed and the laminin receptor binding peptide (YIGSR) was attached to their surface to facilitate targeting. In vitro uptake studies performed under medium flow conditions revealed that the uptake of YIGSR-attached NPs by monolayers of B16 melanoma cells was 2-fold higher compared to the uptake of scrambled peptide-NPs. In cultures of healthy lung cells, the uptake of YIGSR-NPs was low and similar to the uptake of scrambled peptide-NPs. Competition assays using cultured B16 melanoma cells pre-incubated with soluble laminin confirmed that the entry of the YIGSR-modified NPs was mediated via interaction with the laminin receptor. Following intravenous (i.v.) administration into B16 melanoma tumor-bearing mice, targeting of the tumor by the YIGSR-NPs was up to five-fold higher than the scrambled peptide-NPs, with no heart, liver or lung tropism. In an experimental lung metastases model, following i.v. administration the YIGSR-NPs targeted the cancerous metastatic cells in lungs, with nearly no targeting to the healthy lung cells. Collectively, the data indicate that YIGSR-targeted NPs have a potential to be used for systemic delivery of chemotherapeutic drugs for the treatment of metastatic lung cancer.