(Top) Illustration of photothermal-sensitive polymer-coated Au nanocages. (Middle and bottom) Modulation of telomerase activity up and down in vivo.Researchers have developed tiny gold cages coated with a polymer that ‘opens’ and ‘closes’ when triggered by laser light to deliver a cargo of specialized biochemicals that determine the lifespan of cells [Wang et al., Materials Today (2017), doi: 10.1016/j.mattod.2017.07.004].
The team from Changchun Institute of Applied Chemistry and the University of Chinese Academy of Sciences in Beijing, China created cube-shaped nanocages with side lengths of just 50-60 nm. The hollow cages with porous walls are coated with heat-sensitive polymers and loaded with active biochemicals. At a specific laser wavelength, the gold nanocages heat up, causing the polymer coating to collapse and release the cargo. When the laser light is switched off, the polymer recovers and halts any further release.
For the nanocages’ cargo, the researchers chose two transcription factors that modulate the activity of the cellular enzyme, telomerase. This enzyme is vital to cellular function because it is involved in the repair of telomeres, the disposable buffers at the end of chromosomes. Every time a chromosome is replicated during cell division, some material is lost so telomeres become shorter over time. Shorter telomeres are associated with age-related diseases such as atherosclerosis, heart disease, Alzheimer’s, and cancer. But boosting or reactivating telomerase activity promises tissue regeneration, delayed aging, and extended lifespan.
Two transcription factors, Myc and Mad, have opposing effects – one promotes while the other suppresses telomerase activity. Cleverly, the researchers created two types of nanocage by varying the Au/Ag alloy that respond to different wavelengths of light. The novel approach can reduce telomerase activity in cells by releasing the suppressing agent at one wavelength (670 nm) or increase telomerase activity with the promoting agent at a different wavelength (808 nm).
“The concept we have developed is a new method to modulate telomerase activity, not only inhibit or increase it,” points out Xiaogang Qu.
The team demonstrated that the approach also works in vivo with mice. Although the modulation of telomerase activity is not as effective in vivo as in cells, the researchers still showed that near infrared (NIR) illumination at different wavelengths could increase and decrease telomerase activity.
“Our system could be used as an anti-tumor treatment because telomerase is an important biomarker and specific drug-target for tumors,” says Qu. “As telomerase expression relates to tissue development and renewal, this system could also be applied in tissue engineering.”
The approach could pave the way for NIR-based control of gene and protein activity in living systems and provide a new insight into aging and related diseases. But although the work shows great promise, much effort will be needed to apply the approach in the clinic in the future, cautions Qu.