Light-activated nanoparticles could avoid painful eye injections for ‘wet’ macular degeneration

Could intravitreal injections become a thing of the past?

There are two standard treatments for “wet” age-related macular degeneration (AMD), in which abnormal, leaky blood vessels in the back of the eye lead to fluid buildup and vision loss. The first, injection of medication directly into the eye, can be painful and can cause inflammation, infection and detachment of the retina. The second, ablation therapy, uses lasers to destroy the leaky blood vessels. It, too, is unpleasant to undergo, and the lasers can also destroy surrounding healthy tissue, causing further vision loss.

In today’s Nature Communications, the lab of Daniel Kohane, MD, PhD, provides proof-of-concept of a more tolerable alternative: tiny, drug-carrying nanoparticles that can be injected intravenously, but deliver medication only to the eye.

A kinder eye treatment

The particles are activated by a specific wavelength of light where treatment is needed. In addition to AMD, they could also potentially treat other eye diseases involving abnormalities in blood vessels, such as retinopathy of prematurity and diabetic retinopathy.

“The big deal here is that we can just treat the diseased parts of the eye without injecting the drug directly into the eye or impacting the rest of the body,” says Kohane, who heads the Laboratory for Biomaterials and Drug Delivery in the Division of Critical Care Medicine at Boston Children’s Hospital.

A biotech tour-de-force

In addition to medication, each nanoparticle contains two other elements: cell-penetrating peptides (CPPs), which allow it to enter the diseased parts of the eye, and DEACM, a molecule that “hides” the CPPs, preventing the nanoparticles from entering cells. When blue light is applied to the eye that needs treatment, it activates the nanoparticles by cleaving off DEACM, exposing the CPPs. The nanoparticles can then enter the cells and release their medical payload. 

“Through this method, called phototargeting, the affected parts of the eye are treated, but the rest of body has very little exposure to the drug,” says Yanfei Wang, PhD, a research fellow in Kohane’s lab and first author on the paper. The eye is unharmed since it is designed to receive light.

When light is applied, the DEACM molecules (green squares at right) are cleaved off. This exposes the CPPs (black triangles), allowing the nanoparticles to deliver medicine. (CREDIT: KOHANE LAB / BOSTON CHILDREN’S HOSPITAL)

Active and passive targeting

In addition to this active form of targeting, the system also takes advantage of passive targeting. The leaky blood vessels characteristic of wet AMD allow the nanoparticles to passively accumulate in the eye. These areas then have a greater concentration of nanoparticles that can be triggered by light.

In mouse trials, the intravenously injected nanoparticles performed as well as direct injections of “free” medication into the eye. Kohane believes they could be an effective strategy for ocular drug delivery.

“A lot of knobs still need to be tweaked in terms of dosing, but Yanfei has shown it can be done,” he says. 

This is far from the first time the Kohane lab has produced novel drug delivery systems using nanoparticles. Read more on some of the lab’s work with nanoparticles here.

Co-authors on the paper are Tianjiao Ji, Manisha Mehta, Weiping Wang and Elizabeth Marino in the Laboratory for Biomaterials and Drug Delivery and Chi-Hsiu Liu and Jing Chen from Boston Children’s Department of Ophthalmology. The work was supported by the National Institutes of Health.