Biomarker System Offers Advanced Cancer Detection

A combined biomarker and drug delivery system could lead to very localized, more effective cancer treatment.

Developed by researchers at Nanyang Technological University, the biomarker detects and makes visible tumor cells by lighting up under a near-infrared imaging device. It has also demonstrated the ability to release medications to treat cancer in those exact cells.

Coumarin-hemicyanine (CHC1)-modified upconversion nanophosphors, which make up the biomarker, glow under NIR light when tumor cells release a hydrogen sulfide (H₂S) signaling agent. “This inorganic-organic integrated nanoprobe is demonstrated to display a fast response time with a large ratiometric upconversion luminescence (UCL) enhancement, and extraordinary photostability,” the researchers wrote in a study.

NTU associate professors Dr. Zhang Qichun and Dr. Joachim Loo study the differences between the new biomarker and conventional ones. Images courtesy of Nanyang Technological University.

Using conventional downconversion organic fluorescent probes to image H₂S has been shown to be impractical for bioimaging beyond a certain depth because of the short tissue penetration of UV and visible light as an excitation source.

“Near-infrared light can penetrate 3 to 4 cm beyond the skin to deep tissue, much deeper than visible light,” said professor Dr. Zhang Qichun. “It also does not cause any damage to healthy cells, unlike ultraviolet or visible light.”

He added that visible light causes photobleaching (the destruction of the fluorescence dye), as well, a challenge that the new biomarker eliminates.

More effective imaging is not the biomarker’s only capability. It is also able to release anticancer medications via a layer of the drug that coats the outside of the nanoparticle. When NIR light illuminates the biomarker on the tumor cells, those medications are released.

“This is the first time we are able to do bioimaging, and potentially target the delivery of drugs at the same time, as proven in small animal tests,” said professor Dr. Joachim Loo.

The biomarker was also found to be nontoxic; it can stay in the body for up to two days, and passes safely out of the body. It exhibits twice the contrast of conventional dyes and can emit up to three different colors, allowing for advanced distinction between tumor cells and those that are healthy.

The researchers are now looking into the possibility of stacking multiple layers of medications onto the biomarker. They expect that this would reduce side effects for cancer patients “due to the small doses administered and also higher efficacy, as the biomarker has the ability to accurately target tumor cells.”

The work was funded by NTU, Singapore’s Ministry of Education and the National Research Foundation of Singapore. The research was published in Small (doi: 10.1002/smll.201401867).

For more information, visit www.ntu.edu.sg.