Jump to main content
Jump to site search

Issue 10, 2013
Previous Article Next Article

Chemical principles for the design of a novel fluorescent probe with high cancer-targeting selectivity and sensitivity

Author affiliations

Abstract

Understanding of principles governing selective and sensitive cancer targeting is critical for development of chemicals for cancer diagnostics and treatment. We determined the underlying mechanisms of how a novel fluorescent small organic molecule, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC), selectively labels cancer cells but not normal cells. We show that BMVC is retained in the lysosomes of normal cells. In cancer cells, BMVC escapes lysosomal retention and localizes to the mitochondria or to the nucleus, where DNA-binding dramatically increases BMVC fluorescence intensity, allowing it to light up only cancer cells. Structure–function analyses of BMVC derivatives show that hydrogen-bonding capacity is a key determinant of lysosomal retention in normal cells, whereas lipophilicity directs these derivatives to the mitochondria or the nucleus in cancer cells. In addition, drug-resistant cancer cells preferentially retain BMVC in their lysosomes compared to drug-sensitive cancer cells, and BMVC can be released from drug-resistant lysosomes using lysosomotropic agents. Our results further our understanding of how properties of cellular organelles differ between normal and cancer cells, which can be exploited for diagnostic and/or therapeutic use. We also provide physiochemical design principles for selective targeting of small molecules to different organelles. Moreover, our results suggest that agents which can increase lysosomal membrane permeability may re-sensitize drug-resistant cancer cells to chemotherapeutic agents.

Graphical abstract: Chemical principles for the design of a novel fluorescent probe with high cancer-targeting selectivity and sensitivity

Back to tab navigation

Supplementary files

Publication details

The article was received on 19 Mar 2013, accepted on 24 Jul 2013 and first published on 31 Jul 2013


Article type: Paper
DOI: 10.1039/C3IB40058A
Citation: Integr. Biol., 2013,5, 1217-1228
  •   Request permissions

    Chemical principles for the design of a novel fluorescent probe with high cancer-targeting selectivity and sensitivity

    C. Kang, W. Huang, C. Kouh, Z. Wang, C. Cho, C. Chang, C. Wang, T. Chang, J. Seemann and L. J. Huang, Integr. Biol., 2013, 5, 1217
    DOI: 10.1039/C3IB40058A

Search articles by author

Spotlight

Advertisements