Glowing Nanoparticles Control Biological Processes

Nanoparticles and superballs can emit different colours of light when excited by lasers at different wavelengths. The novel nanoparticles fluoresce either red or green depending on the energy of infrared light used to excite them. These different colours of light can then be used to trigger specific biological processes. (Source: NUS)

The biological technique of opto­genetics uses light to control cells within living tissues that have been genetically modified to be light-sensitive. However, deeply pene­trating light is often needed to activate the genes in living tissues and there is limited control of processes like this, as the nano­particle used for acti­vation would activate several genes at once. Now, researchers from the National Uni­versity of Singa­pore NUS have developed a method to give more control to this process, by using specially designed nano­particles and nano­clusters. These nano­particles and superballs can emit different colours of light when excited by lasers at different wave­lengths. These different colours of light can then be used to trigger specific bio­logical processes.

To activate light-sensi­tive genes, the team led by Yong Zhang from the Department of Biomedical Engineering at NUS, used the nano­particles and superballs to upconvert near-infrared (NIR) light to higher energies of visible light. Since NIR light is deeply pene­trating, this approach may be used for many deep-seated tissue treatments. Zhang and his team invented new nano­particles that emit either red or green light, depending on the wave­length of the NIR radiation used to excite them. The nano­particles radiate red light when excited by a laser beam with a wavelength of 980 nanometers, and green light when the laser beam’s wavelength is decreased to 808 nano­meters.

In addition to being two different colours, the light emitted from these nanoparticles can be used for bi-directional acti­vation. This is different from current opto­genetic therapies using nano­particles, which can only activate in a mono­directional fashion. “As such, we can intricately mani­pulate a biological process, or some steps in the process, in different directions or programma­tically,” explained Zhang. The researchers showed that it was possible to use these particles to control the beating rate in modified heart-muscle cells. By optically controlling two light-activated channels known as Jaws and VChR1 in the same cell, they were able to alter the speed of the heartbeat. The red light slowed down the heartrate, and the green light sped it up.

These nano­particles consist of an inner core which is rich in erbium, surrounded by layers of ytterbium and neodymium-doped materials. “For generating such orthogonal fluores­cence emissions, we usually need to dope multiple lanthanide ions into the nano­crystals. In our study, this is achieved by using one ion only.” This inno­vation from the researchers ensures that the orthogonal emissions all come from erbium ions. In regards to this material breakthrough and appli­cation innovation, Zhang stated, “This demons­tration provides a major step forward towards program­mable multi-directional pathway control, and also offers intriguing oppor­tunities for appli­cations in many other synergis­tically interactive biological processes such as diag­nostics and therapies.”

In addition to the novel nano­particles, Zhang and his team recently synthesised clusters of two different nano­particles which they named superballs. In a similar way to the novel nano­particles, these superballs emit different coloured light when excited with different wavelengths of NIR radiation. They radiate red light when excited by a laser beam with a wavelength of 980 nanometers, and UV/blue light when the laser beam’s wavelength is decreased to 808 nanometres. These novel superballs were then used to enhance a photo­dynamic cancer treatment procedure.

When the superballs were energe­tically excited to radiate red light they were able to enter a cell. Next, they were excited to radiate UV/blue light to increase cell’s sensi­tivity to reactive oxygen species. Finally, they were excited to radiate red light again to activate photo­sensitive drugs to produce reactive oxygen species. These reactive oxygen species can then induce the killing of tumour cells. With this research break­through, the scientists have developed a simple, user-friendly method for synthesising these superballs. The shape, size and even the exci­tation/emission wavelengths of the superballs can be modified depending on the application needed.

The applications of these nano­particles and super­balls are numerous. “This will be of interest to biologists and clinicians in different fields, especially those working on photo­therapy, including photo­dynamic therapy, photothermal therapy, light controlled drug/gene delivery, and opto­genetics,” said Zhang. For the next stages of research, he stated, “Ultimately, the objective of this project is to use wireless elec­tronics together with nano­particles for enhanced photo­dynamic therapies which can treat large tumours in deep tissues.” As such, the researchers will continue to develop novel materials and invent innovative appli­cations in this area. (Source: NUS)

Reference: Z. Zhang et al.: Upconversion superballs for programmable photoactivation of therapeutics, Nat. Commun. 10, 4586 (2019); DOI: 10.1038/s41467-019-12506-w

Link: Faculty of Engineering, Dept. of Biomedical Engineering, National University of Singapore, Singapore, Singapore

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