LAT1-Targeting Thermoresponsive Liposomes for Effective Cellular Uptake by Cancer Cells

Minami Maekawa-Matsuura, Kei Fujieda, Yutaro Maekawa, Tomohiro Nishimura, Kenichi Nagase, Hideko Kanazawa

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


L-type amino acid transporter 1 (LAT1) is a transporter that is more highly expressed in cancer cells compared with normal cells. In the present study, liposomes, composed of egg phosphatidylcholine (EPC) and dioleoyl phosphatidylethanolamine, were modified with LAT1-targeting thermoresponsive polymer, l-tyrosine-conjugated poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)). The cellular uptake of the prepared LAT1-targeting liposomes was evaluated using HeLa cells as a cancer cell model. At temperatures above the polymer's lower critical solution temperature, uptake of the liposomes into cells was observed because the polymer at the liposome surface became hydrophobic and interacted with the cell membrane. Flow cytometry analysis suggested that l-tyrosine-P(NIPAAm-co-DMAAm)-liposomes exhibited markedly increased cellular uptake by HeLa cells compared with that of liposomes not modified with l-tyrosine. This result indicated that cellular uptake of liposomes can be enhanced by the affinity between l-tyrosine and the LAT1 of HeLa cells. The developed functional liposomes, which exhibit both thermoresponsive and LAT1-targeting properties, would be appropriate for temperature-modulated drug delivery and imaging with good targeting ability.

Original languageEnglish
Pages (from-to)6443-6451
Number of pages9
JournalACS Omega
Issue number4
Publication statusPublished - 2019 Apr 8

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering


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