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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1219-1227
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number3
DOIs
Publication statusPublished - 2017 Apr 1

Fingerprint

Liposomes
Cells
Breast Neoplasms
Doxorubicin
Pharmaceutical Preparations
Immunoglobulin Fab Fragments
Antibodies
Tumors
Bearings (structural)
Drug Delivery Systems
Cytotoxicity
Drug delivery
Encapsulation
Lipids
Polyethylene glycols
Inhibitory Concentration 50
Glutamic Acid
Neoplasms
Growth

Keywords

  • Anticancer
  • Drug delivery system
  • ErbB2-antibody
  • Immunoliposomes
  • pH-sensitive

ASJC Scopus subject areas

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

Cite this

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title = "Construction and evaluation of pH-sensitive immunoliposomes for enhanced delivery of anticancer drug to ErbB2 over-expressing breast cancer cells",
abstract = "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.",
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T1 - Construction and evaluation of pH-sensitive immunoliposomes for enhanced delivery of anticancer drug to ErbB2 over-expressing breast cancer cells

AU - Li, Tianshu

AU - Amari, Takuya

AU - Senba, Kentaro

AU - Yamamoto, Tadashi

AU - Takeoka, Shinji

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