Folate-based near-infrared fluorescent theranostic gemcitabine delivery

Zhigang Yang, Jae Hong Lee, Hyun Mi Jeon, Ji Hye Han, Nayoung Park, Yanxia He, Hyunseung Lee, Kwan Soo Hong, Chulhun Kang, Jong Seung Kim

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

A series of heptamethine cyanine (1-3) derivatives bearing a carbamate ethyl disulfide group and gemcitabine, an anticancer drug, have been newly synthesized. Their disulfide bonds are readily cleaved by various thiols including glutathione, to result in a subsequent decomposition of the carbamate into amine followed by release of the active gemcitabine, which can be monitored by the fluorescence changes. In the biological experiment, prodrug 1 is preferentially up-taken by folate-positive KB cells over folate-negative A549 cells via receptor-mediated endocytosis to release gemcitabine causing cell death and to emit fluorescence in endoplasmic reticulum. Moreover, it is selectively accumulated in the KB cells which were treated to mice by dorsal subcutaneous injection. This drug delivery system is a new theranostic agent, wherein both therapeutic effect and drug uptake can be easily monitored at the subcellular level, by in vivo and in vitro fluorescence imaging.

Original languageEnglish
Pages (from-to)11657-11662
Number of pages6
JournalJournal of the American Chemical Society
Volume135
Issue number31
DOIs
Publication statusPublished - 2013 Aug 7

Fingerprint

gemcitabine
Folic Acid
KB Cells
Fluorescence
Infrared radiation
Disulfides
Bearings (structural)
Carbamates
Optical Imaging
Urethane
Prodrugs
Therapeutic Uses
Cell death
Subcutaneous Injections
Drug Delivery Systems
Endocytosis
Sulfhydryl Compounds
Endoplasmic Reticulum
Pharmaceutical Preparations
Amines

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Folate-based near-infrared fluorescent theranostic gemcitabine delivery. / Yang, Zhigang; Lee, Jae Hong; Jeon, Hyun Mi; Han, Ji Hye; Park, Nayoung; He, Yanxia; Lee, Hyunseung; Hong, Kwan Soo; Kang, Chulhun; Kim, Jong Seung.

In: Journal of the American Chemical Society, Vol. 135, No. 31, 07.08.2013, p. 11657-11662.

Research output: Contribution to journalArticle

Yang, Z, Lee, JH, Jeon, HM, Han, JH, Park, N, He, Y, Lee, H, Hong, KS, Kang, C & Kim, JS 2013, 'Folate-based near-infrared fluorescent theranostic gemcitabine delivery', Journal of the American Chemical Society, vol. 135, no. 31, pp. 11657-11662. https://doi.org/10.1021/ja405372k
Yang, Zhigang ; Lee, Jae Hong ; Jeon, Hyun Mi ; Han, Ji Hye ; Park, Nayoung ; He, Yanxia ; Lee, Hyunseung ; Hong, Kwan Soo ; Kang, Chulhun ; Kim, Jong Seung. / Folate-based near-infrared fluorescent theranostic gemcitabine delivery. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 31. pp. 11657-11662.
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