Construction and evaluation of pH-sensitive immunoliposomes for enhanced delivery of anticancer drug to ErbB2 over-expressing breast cancer cells

Tianshu Li, Takuya Amari, Kentaro Senba, Tadashi Yamamoto, Shinji Takeoka

研究成果: Article

16 引用 (Scopus)

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1,5-Dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG) liposomes were previously developed to enhance drug delivery efficiency in tumor cells owing to its pH-responsive properties. Herein, we report the modification of GGLG liposomes by conjugating a Fab′ fragment of an ErbB2 antibody to the terminus of PEG (polyethylene glycol)-lipid (Fab′-GGLG liposomes). The conjugation of Fab′ fragments did not affect the antibody activity, drug (doxorubicin, DOX) encapsulation efficiency, stability during storage or pH-sensitivity. However, the binding affinity of Fab′-GGLG liposomes was enhanced to ErbB2-overexpressing HCC1954 cells specifically, and the cell association increased 10-fold in comparison to GGLG liposomes. Consequently, intracellular DOX delivery was enhanced, with an increased cytotoxicity in HCC1954 cells (i.e., IC50 of 1.17 and 3.08 μg/mL for Fab′-GGLG-DOX and GGLG-DOX liposomes, respectively). Further, a significantly enhanced tumor growth inhibition was obtained in an ErbB2-overexpressing breast cancer-bearing mouse model. Therefore, a potent anticancer drug delivery system was constructed by the immunological modification of pH-sensitive liposomes.

元の言語English
ページ(範囲)1219-1227
ページ数9
ジャーナルNanomedicine: Nanotechnology, Biology, and Medicine
13
発行部数3
DOI
出版物ステータスPublished - 2017 4 1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering
  • Molecular Medicine
  • Materials Science(all)
  • Pharmaceutical Science

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