RRC ID 55892
Author Matsuura M, Ohshima M, Hiruta Y, Nishimura T, Nagase K, Kanazawa H.
Title LAT1-Targeting Thermoresponsive Fluorescent Polymer Probes for Cancer Cell Imaging.
Journal Int J Mol Sci
Abstract L-type amino acid transporter 1 (LAT1) is more highly expressed in cancer cells compared with normal cells. LAT1 targeting probes would therefore be a promising tool for cancer cell imaging. In this study, LAT1-targeting thermoresponsive fluorescent polymer probes based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) were synthesized and their affinity for LAT1 was evaluated. The synthesized polymer probes interacted with LAT1 on HeLa cells, and inhibition of l-[³H]-leucine, one of the substrates for LAT1 uptake, was investigated. l-Tyrosine-conjugated P(NIPAAm-co-DMAAm) inhibited the uptake of l-[³H]-leucine, while P(NIPAAm-co-DMAAm) and l-phenylalanine-conjugated P(NIPAAm-co-DMAAm) did not. This result indicated that l-tyrosine-conjugated polymer has a high affinity for LAT1. The fluorescent polymer probes were prepared by modification of a terminal polymer group with fluorescein-5-maleimide (FL). Above the polymer transition temperature, cellular uptake of the polymer probes was observed because the polymers became hydrophobic, which enhanced the interaction with the cell membrane. Furthermore, quantitative analysis of the fluorescent probe using flow cytometry indicated that l-tyrosine-conjugated P(NIPAAm-co-DMAAm)-FL shows higher fluorescence intensity earlier than P(NIPAAm-co-DMAAm)-FL. The result suggested that cellular uptake was promoted by the LAT1 affinity site. The developed LAT1-targeting thermoresponsive fluorescent polymer probes are expected to be useful for cancer cell imaging.
Volume 19(6)
Published 2018-6-1
DOI 10.3390/ijms19061646
PII ijms19061646
PMID 29865203
PMC PMC6032285
MeSH Acrylamides / chemistry Fluorescent Dyes / chemistry Fluorescent Dyes / metabolism* HeLa Cells Hot Temperature Humans Hydrophobic and Hydrophilic Interactions Large Neutral Amino Acid-Transporter 1 / chemistry Large Neutral Amino Acid-Transporter 1 / drug effects Large Neutral Amino Acid-Transporter 1 / metabolism* Leucine / metabolism Molecular Imaging / methods* Neoplasms / diagnostic imaging* Neoplasms / metabolism Polymers / chemistry Polymers / metabolism*
IF 4.183
Times Cited 8
Human and Animal Cells 293(RCB1637)