If the war on cancer is won – finally – someday, a team of scientists and students in the joint biomedical engineering program at N.C. State and UNC-Chapel Hill could be a significant reason. But their technology approach is different than the high-profile nanotech program developed by Dr. Joseph Simone, who also teaches at UNC and NCSU, and Liquidia, which is based on his research. In an exclusive interview with WRALTechWire, the lead author of a new paper describes the potentially big breakthrough using small, small particles.

Dr. Zhen Gu, an assistant professor in the joint biomedical engineering program who is focused on pharmacoengineering research, says the team has been working on the concept of using nanoparticles to deliver what he calls “programmed” cancer therapy for about a year and a half. They have already filed a patent on their idea, are looking for grants to support further reasearch, and are even contemplating starting their own company. The paper was published in Advanced Functional Materials.

“The early results are very promising, and we think this could be scaled up for large-scale manufacturing,” Gu says. 

The “secret sauce” for their efforts is a means to create particles containing specific drugs that target specific cancers; as one drug is peeled away by the cancer, another drug is delivered, triggering cancer “cell death.”

The subject of the paper is tests conducted on mice with breast cancer. The particles are designed to fool cancer cells that have developed resistance to chemotherapy, Gu explains. The tests produced “significant improvement” in tumor reduction vs. conventional treatment. 

Our Q&A:

I understand that your research is separate than that conducted by Dr. Joseph Simone and his work in nanotechnology for drug delivery as being pursued at local firm Liquidia. The technology is called PRINT, as I am sure you know. How does your technology and approach differ from that of Dr. Simone?

Joe is my friend. His method is based on a template or mold to obtain uniform nanoparticles for drug delivery.

Our method is based on self-assembly and “interfacial polymerization” to encapsulate drugs. So different fabrication methods.

In a more detailed explanation provided by NCSU, Gu described the process:

“Cancer cells can develop resistance to chemotherapy drugs, but are less likely to develop resistance when multiple drugs are delivered simultaneously.

“However, different drugs target different parts of the cancer cell. For example, the protein drug TRAIL is most effective against the cell membrane, while doxorubicin (Dox) is most effective when delivered to the nucleus. We’ve come up with a sequential and site-specific delivery technique that first delivers TRAIL to cancer cell membranes and then penetrates the membrane to deliver Dox to the nucleus.”

Is your research patent protected or is intellectual property protection effort underway?

Yes, we have already filed a patent on this

If proven over time how long could it be before testing is conducted in humans?

We will further optimize our formulation and test on large animals first then step into clinical trials. [It] may take a few years.

It would appear that this technology could also work against other types of cancer? And if so could we be looking at a significant breakthrough in the decades-long war against cancer?

Yes. This is our proof-of-concept, which successfully demonstrated that two or multiple drugs can be delivered into different parts of cancer cells and achieve synergistic anticancer functions. It is one more step to achieve “programmed” cancer therapy.

What are the next steps for testing?

Optimize formulations and test on monkeys (if grants are ready)

Have you reached out to any potential partners in the private sector and/or the federal government for assistance in funding?

We are now applying for potential grants from different age

Could this technology some day be licensed to the private sector or are you contemplating starting a company focused on this?

We consider both. My students really want to run a start-up company using our own technology.

Gu’s background

By the way, Gu brings a diversified and growing academic resume to the project:

  • Postdoc, Chemical Engineering, Koch Institute, Massachusetts Institute of Technology | Harvard Medical School
  • Ph.D., School of Engineering and Applied Science, University of California, Los Angeles
  • M.S., Polymer Science and Engineering, Nanjing University
  • B.S., Chemistry, Nanjing University


“Gel–Liposome-Mediated Co-Delivery of Anticancer Membrane-Associated Proteins and Small-Molecule Drugs for Enhanced Therapeutic Efficacy”

Authors: Tianyue Jiang, Ran Mo, and Zhen Gu, North Carolina State University and University of North Carolina at Chapel Hill; Adriano Bellotti, North Carolina State University; Jianping Zhou, China Pharmaceutical University.

Published: Online Jan. 2, 2014, Advanced Functional Materials

Abstract: A programmed drug-delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core–shell-based “nanodepot” consisting of a liposomal core and a crosslinked-gel shell (designated Gelipo) is developed for the sequential and site-specific delivery (SSSD) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin (Dox). As a small-molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half-maximal inhibitory concentration (IC50) of TRAIL and Dox co-loaded Gelipo (TRAIL/Dox-Gelipo) toward human breast cancer (MDA-MB-231) cells is 83 ng mL–1 (Dox concentration), which presents a 5.9-fold increase in the cytotoxicity compared to 569 ng mL–1 of Dox-loaded Gelipo (Dox-Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA-MB-231 xenograft tumor animal model.