Biomedical engineering researchers at North Carolina State University (NC State) and the University of North Carolina at Chapel Hill (UNC Chapel Hill) have developed a technique that uses a patch embedded with microneedles to deliver cancer immunotherapy treatment directly to the site of melanoma. In animal studies, the technique more effectively targeted melanoma than other immunotherapy treatments. These findings were published by Wang et al in Nano Letters.
Recently, cancer immunotherapy research has focused on using anti–programmed cell death protein 1 (PD-1) antibodies.
“However, this poses several challenges,” said Chao Wang, PhD, a postdoctoral researcher in the joint Biomedical Engineering Program at NC State and UNC Chapel Hill. “First, the anti–PD-1 antibodies are usually injected into the bloodstream, so they cannot target the tumor site effectively. Second, the overdose of antibodies can cause side effects such as an autoimmune disorder.”
Composition of Microneedle Patch
To address these challenges, the researchers developed a patch that uses microneedles to deliver anti–PD-1 antibodies locally to the skin tumor. The microneedles are made from hyaluronic acid, a biocompatible material.
The anti–PD-1 antibodies are embedded in nanoparticles, along with glucose oxidase—an enzyme that produces acid when it comes into contact with glucose. These nanoparticles are then loaded into microneedles, which are arrayed on the surface of a patch.
When the patch is applied to a melanoma, blood enters the microneedles. The glucose in the blood makes the glucose oxidase produce acid, which slowly breaks down the nanoparticles. As the nanoparticles degrade, the anti–PD-1 antibodies are released into the tumor.
“This technique creates a steady, sustained release of antibodies directly into the tumor site; it is an efficient approach with enhanced retention of anti–PD-1 antibodies in the tumor microenvironment,” said Zhen Gu, PhD, an Assistant Professor in the joint Biomedical Engineering Program.
The researchers tested the technique against melanoma in a mouse model. The microneedle patch loaded with anti–PD-1 nanoparticles was compared to treatment by injecting anti–PD-1 antibodies directly into the bloodstream and to injecting anti–PD-1 nanoparticles directly into the tumor.
“After 40 days, 40% of the mice who were treated using the microneedle patch survived and had no detectable remaining melanoma—compared to a 0% survival rate for the control groups,” said Yanqi Ye, a PhD student in Dr. Gu's laboratory.
The researchers also created a drug cocktail, consisting of anti–PD-1 antibodies and another antibody, anti–CTLA-4.
“Using a combination of anti–PD-1 and anti–CTLA-4 in the microneedle patch, 70% of the mice survived and had no detectable melanoma after 40 days,” Dr. Wang said.
“Because of the sustained and localized release manner, mediated by microneedles, we are able to achieve desirable therapeutic effects with a relatively low dosage, which reduces the risk of autoimmune disorders,” Dr. Gu said.
“We're excited about this technique, and are seeking funding to pursue further studies and potential clinical translation,” Dr. Gu concluded.
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