CMU Researchers Develop Method for Customizable, Targeted Drug Delivery

Cells naturally send tiny packages to one another to share information. Researchers at Carnegie Mellon University have developed a simple, low-cost way to turn those packages into drug carriers that can deliver treatments directly to cancer cells, potentially improving effectiveness while reducing side effects. 

“Modern anti-cancer drugs are strong already. What we really need is precision. So, how do we deliver things to cells precisely? I believe that the best solution is the one that nature has already made for us,” said Christopher Blum, a Ph.D. candidate in the Department of Chemistry. 

Blum developed a new platform that modifies naturally occurring cellular transport vesicles so they can deliver therapeutic cargo to specific cells while avoiding unintended targets. The research was published in ACS Applied Bio Materials(opens in new window). 

Many cells produce tiny bubble-like structures called extracellular vesicles (EVs) that carry proteins, nucleic acids and other molecules throughout the body. Because EVs are the body’s natural cargo carriers, researchers see them as promising vehicles for delivering drugs to treat cancer, neurological disorders, cardiovascular disease and other conditions. 

Despite their potential, engineering EVs for drug delivery has been challenging. EVs can be absorbed by many different cell types, causing them to accumulate in non-target tissues. This limits their effectiveness as targeted therapies. At the same time, modifying EVs for targeted delivery is often expensive and technically complex. 

The Carnegie Mellon team’s new platform, called EZON (Easy OligoNucleotide) EV modification, addresses both problems at once. The system helps prevent EVs from binding to the wrong cells while guiding them to specific targets. 

“EZON represents an advance in nanoscale surface engineering, and it has direct therapeutic relevance and broad applicability across EV sources and cargo types,” said Subha Das, associate professor of chemistry in the Mellon College of Science. “Given the platform’s simplicity, any researcher working with mammalian EVs can deploy EZON using commercially available, unmodified oligonucleotides in a single afternoon.” 

The system relies on a specially designed DNA tether with two functions. One end acts as an anchor that attaches to proteins on the EV surface and helps prevent it from sticking to the wrong cells. The other end acts like an address label, helping the engineered EV recognize and attach to specific cancer cells.

The approach is highly adaptable. By changing part of the DNA sequence, researchers can redirect EVs to different cell types, expanding the technology’s potential far beyond a single form of cancer.

“I think for me, the exciting part is the flexibility of it,” Blum said. “The design is modular, allowing you to choose which display strand works best for the job at hand. Not only does this open the pathway to a variety of different cancer treatments, but it also opens the door toward non-cancerous targets, letting you do things like treat immune diseases and more.”

With EZON, the EV-modification process takes just a few hours and uses readily available materials. EZON also offers significant cost reduction compared with many existing EV-engineering methods while maintaining the flexibility needed for a wide range of therapeutic applications.

Blum and Das hope the technology will accelerate the development of more precise treatments for cancer and other diseases while making EV-based therapies easier and less expensive to produce.

As a chemist working in an interdisciplinary research area, Blum drew on the expertise of faculty in Biological Sciences and Biomedical Engineering, including Research Professor Phil Campbell, Associate Professor Tagbo Niepa, and Assistant Professors Elizabeth Ransey and Jonathan Henninger.