Light-Guided Hydrogels Could Aid Drug Delivery

National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD

Light therapy has been used to treat a number of disorders, including psoriasis, and highly targeted lasers have been used for specific skin disorders, eye diseases, or cancers. Advances in imaging methods and equipment can now allow scientists to see the effects of light at the cellular level, which could lead to ways to use specific types of light for more even complex and direct manipulation of individual cells.

Fig. 1 – A mouse with a hydrogel implant and fiber optic cable. The blue light delivered through the cable is evenly distributed by the hydrogel. (Credit: Seok-Hyun Yun, Harvard Medical School)

Optogenetics is a relatively new technique that harnesses light to activate or inhibit light-responsive proteins controlling specific cell functions. For most proposed clinical uses, light needs to be delivered evenly across a number of cells to have a reproducible therapeutic effect, but human tissue is not transparent and scatters, absorbs, or otherwise reduces light penetration, reducing the ability to deliver light below the skin.

To address this delivery challenge, researchers at Harvard Medical School, along with scientists at several institutions in Korea, experimented with using optogenetics in combination with transparent hydrogels, which are being researched for use in medical implants.

Currently, most medical implants are made with rigid materials like plastic and metal, which placed among relatively soft tissues can cause inflammation and other unwanted side effects. In contrast, hydrogels can be easily constructed using more biocompatible materials, and their high water content and flexible nature may conform more closely to muscles, organs, and other internal body parts so that light is guided efficiently, the researchers say. In addition, some fluids can flow through hydrogels, which may allow for different types of uses than can be achieved with implants made of conventional, impermeable materials.

A Glowing Report

Experimenting with the hydrogel recipe, Harvard researcher Seok-Hyun Andy Yun, PhD, and colleagues devised a strong yet flexible, clear hydrogel slab able to guide a laser beam. They also seeded the hydrogel with cells that refract and scatter light, creating a uniform glow throughout the slab.

When lit by a fiber optic and implanted just under the skin in mice, the glowing hydrogel could be clearly seen. (See Figure 1) In a follow-up experiment, the researchers grew cells that glow green in the presence of cadmium, a toxic heavy metal often used to make quantum dot sensors. When cadmium-core quantum dots were injected into mice with hydrogel implants, the cells within the hydrogel glowed green. However, when dots with a more biocompatible zinc-based coating were injected, the hydrogel did not glow, suggesting that the zinc coating effectively shielded the cells in the hydrogel from cadmium toxicity.

To test the material’s ability to deliver a treatment, the researchers created slabs embedded with cells that glow in the presence of calcium. The slabs were then fitted with a blue light fiber optic and implanted in mice with chemically induced diabetes. When exposed to blue light, a protein called melanopsin set off a cascade of activity within the cells, including releasing the calcium to help to control diabetic effects.

In mice exposed to the blue light, the cells in the implanted hydrogel glowed much more compared to hydrogels in unexposed mice, suggesting the former group had higher levels of intracellular calcium and anti-diabetic activity. To further validate this finding, the mice were given a glucose tolerance test to see how long it took for their blood sugar levels to return to normal. The light-exposed diabetic mice achieved regular blood sugar levels within an hour and a half, while the untreated diabetic mice continued to have elevated blood sugar even after two hours, indicating that light delivered via the hydrogel produced a measurable biological effect and could someday be used to deliver optogenetic treatments.