Issue 11, 2016

Small molecule additive enhances cell uptake of 5-aminolevulinic acid and conversion to protoporphyrin IX

Abstract

Administration of exogenous 5-aminolevulinic acid (5-ALA) to cancerous tissue leads to intracellular production of photoactive protoporphyrin IX, a biosynthetic process that enables photodynamic therapy and fluorescence-guided surgery of cancer. Cell uptake of 5-ALA is limited by its polar structure and there is a need for non-toxic chemical additives that can enhance its cell permeation. Two zinc-bis(dipicolylamine) (ZnBDPA) compounds were evaluated for their ability to promote uptake of 5-ALA into Chinese Hamster Ovary (CHO-K1) cells and produce protoporphyrin IX. One of the ZnBDPA compounds was found to be quite effective, and a systematic comparison of cells incubated with 5-ALA (100 μM) for 6 hours showed that the presence of this ZnBDPA compound (10 μM) produced 3-fold more protoporphyrin IX than cells treated with 5-ALA alone. The results of mechanistic studies suggest that the ZnBDPA compound does not interact strongly with the 5-ALA. Rather, the additive is membrane active and transiently disrupts the cell membrane, permitting 5-ALA permeation. The membrane disruption is not severe enough to induce cell toxicity or allow passage of larger macromolecules like plasmid DNA.

Graphical abstract: Small molecule additive enhances cell uptake of 5-aminolevulinic acid and conversion to protoporphyrin IX

Article information

Article type
Paper
Submitted
16 May 2016
Accepted
04 Oct 2016
First published
07 Oct 2016

Photochem. Photobiol. Sci., 2016,15, 1408-1416

Small molecule additive enhances cell uptake of 5-aminolevulinic acid and conversion to protoporphyrin IX

K. M. Harmatys, A. J. Musso, K. J. Clear and B. D. Smith, Photochem. Photobiol. Sci., 2016, 15, 1408 DOI: 10.1039/C6PP00151C

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