One of the crucial roles of
tumor extracellular matrix is to act as a barrier to drug delivery. In this study, we analyzed the relationship between the formation of
tumor extracellular matrix and the efficiency of intracellular uptake of
oligonucleotides in human
osteosarcoma cell lines, HOS, and MG-63.
Oligonucleotides used in this study were
nuclear factor-kappa B (
NF-kappaB) decoy, which might be a therapeutic tool for
neoplasms. Pericellular matrix formation was examined by particle exclusion assay. Cellular uptake of
fluorescein isothiocyanate-labeled
NF-kappaB decoy was evaluated by fluorescent microscopy and flow cytometry. Effects of
NF-kappaB decoy on cell viability and cell cycle arrest in MG-63 cells were determined by MTT assay and flow cytometry, respectively. MG-63 cells exhibited abundant pericellular matrix with time compared with HOS cells. Uptake of
fluorescein isothiocyanate-labeled
NF-kappaB decoy decreased in MG-63 cells with time but not in HOS cells in both monolayer and three-dimensional culture using
matrigel. However, after enzymatic removal of pericellular matrix, the uptake markedly recovered in MG-63 cells.
NF-kappaB decoy inhibited cell proliferation and induced G0/G1 cell cycle arrest in MG-63 cells. These results suggest that abundant pericellular matrix might disturb the uptake of
NF-kappaB decoy, and modification of pericellular matrix composition would increase the efficacy of exogenous
oligonucleotides treatment for
neoplasms.