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.