NPG Asia Materials research highlight | doi:

Biomedicine: Smart therapy

Photodynamic therapy is a cancer treatment during which sensitizer dyes are first administered intravenously to the patient then irradiated with light of the appropriate wavelength.  Sensitizer dyes are compounds that readily undergo photoexcitation and sensitize other molecules through energy transfer.  When relaxing to their original state, the excited dyes transfer energy to molecular oxygen in tissue and generate singlet oxygen, which reacts rapidly with neighbouring biomolecules to ultimately kill the tumour cells. 

Tumour cells contain relatively high concentrations of sodium ions and protons. Now, Engin Akkaya and colleagues¹ at Bilkent University in Ankara, Turkey have designed a sensitizer which increases its own singlet oxygen production depending on the local concentrations of these physiologically relevant ions, leading to a new autonomously regulated system.

In the synthesis of their sensitizer, the researchers started with a sodium-selective crown ether—a poly-oxygenated ring—to build a fluorescent dye to which they then appended acid-sensitive pyridine moieties, which are cyclic hydrocarbons containing a nitrogen atom. Spectroscopic studies showed the resulting sensitizer produced singlet oxygen only when sodium ions and protons were both present, suggesting both ions were needed for maximum efficiency.

According to the researchers, several processes including electron and energy transfer compete during the sensitizer de-excitation (Fig. 1).  Sodium binding to the sensitizer blocks electron transfer in favour of energy transfer, thus promoting singlet oxygen production and tumour cell death.  “Increasing the concentration of sodium ions increased the rate of singlet oxygen generation,” says Akkaya. 

Also, protonating the pyridine units caused a red shift in the absorption spectrum.  “This shift moves the absorption peak to the peak emission wavelength of the LED used in the excitation,” says Akkaya. “Thus, the sensitizers are more efficiently excited in the presence of acid.”

The researchers are currently designing more realistic sensory units for future autonomously regulated drug delivery systems.  “Although this is a proof of principle study, we have firmly established the fact that molecular logic holds a greater promise than previously recognized,” says Akkaya  “We believe that with a clear understanding of this potential, truly intelligent drugs will very likely to follow this work.”

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