Nano Superballs Offer Refined Control Of Optogenetics

New nanoparticles and nanoclusters dubbed “superballs” offer more control to optogenetics. Optogenetics is a technique that uses light to control cells within living tissue.

The biological technique controls cells in tissues genetically modified for light sensitivity. Drawbacks are that the light can activate several genes at once and that it must penetrate deeply to be effective.

The new nanoparticles and superballs can emit different colors of light when lasers at different wavelengths excite them. These different colors of light can then trigger specific biological processes.

Upconverting Light

To activate light-sensitive genes, the team led by Zhang Yong, a professor in Biomedical Engineering at the National University of Singapore, used the nanoparticles and superballs to “upconvert” near-infrared (NIR) light to higher energies of visible light[1]. Since NIR light is profoundly 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 decreases to 808 nanometers.

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.

Nanoparticle Superballs

The red light slowed down the heart rate, and the green light sped it up. These nanoparticles consist of an inner core that is rich in erbium, surrounded by layers of ytterbium and neodymium-doped materials.

In addition to the novel nanoparticles, Zhang and his team recently synthesized clusters of two different nanoparticles, which they named “superballs.” In a similar way to the novel nanoparticles, these superballs emit different colored light when excited with varying wavelengths of NIR radiation[2].

Simplified mechanisms of the nanoparticles and superballs

Simplified mechanisms of the nanoparticles and superballs.
Credit: NUS News

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 decreases to 808 nanometers.

The researchers then used these novel superballs 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 emit UV/blue light to increase the 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 tumor cells.

Enhanced Photodynamic Therapies

With this research breakthrough, scientists have developed a simple, user-friendly method for synthesizing these superballs. The shape, size, and the excitation/emission wavelengths of the superballs are modifiable depending on the application.

The nanoparticles and superballs

“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,”

says Zhang.

“Ultimately, the objective of this project is to use wireless electronics together with nanoparticles for enhanced photodynamic therapies which can treat large tumors in deep tissues.”

The research will continue in that direction.

[1] Qingsong Mei, Akshaya Bansal, Muthu Kumara Gnanasammandhan Jayakumar, Zhiming Zhang, Jing Zhang, Hua Huang, Dejie Yu, Chrishan J. A. Ramachandra, Derek J. Hausenloy, Tuck Wah Soong & Yong Zhang. Manipulating energy migration within single lanthanide activator for switchable upconversion emissions towards bidirectional photoactivation. Nat  Commun volume 10, Article number: 4416 (2019)

[2] Zhen Zhang, Muthu Kumara Gnanasammandhan Jayakumar, Xiang Zheng, Swati Shikha, Yi Zhang, Akshaya Bansal, Dennis J. J. Poon, Pek Lim Chu, Eugenia L. L. Yeo, Melvin L. K. Chua, Soo Khee Chee & Yong Zhang. Upconversion superballs for programmable photoactivation of therapeutics. Nat Commun 10, 4586 (2019) doi:10.1038/s41467-019-12506-w