Researchers explain how nanodevices can fight cancer

The antibodies are gradually released in small doses through the NDES implant – a stainless-steel drug reservoir that features membrane-like nanochannels that can diffuse the drug without the need for injections, which often lead to unwanted side effects. 

In experiments on rodents, the procedure has brought a reduction in tumor sizes at doses that are four times less than traditional immunotherapy treatments.

Significant tumor reduction achieved

In a press release, Corrine Ying Xuan Chua, Ph.D., the study’s co-corresponding author and assistant professor of nanomedicine at Houston Methodist Academic Institute, explained that what’s exciting about their findings is that while the NDES device was inserted into just one of two tumors in the animal it was tested on, the researchers saw shrinking both tumors, including in the tumor that didn’t have the device. "This means that local treatment with immunotherapy was able to activate the immune response to target other tumors,” shared the scientist. One of the animals in the study stayed tumor-free for 100 days – the duration of the observation period.

This promising development can’t come too soon for pancreatic cancer patients, 85% of whom get the diagnosis when the disease is already at an advanced stage. Another positive aspect of the research is that it allows doctors treating this type of cancer to focus the delivery of the medicines directly into the tumors, avoiding long-lasting side effects that come with immunotherapy being administered to the patient’s entire body. This way, the patient is less exposed to toxic drugs and potential infections, leading to a higher quality of life.

Nanotechnology fighting cancers

Cancer is a leading cause of death around the world, accounting for nearly one in six deaths. In 2023, around 2 million people will be diagnosed with cancer in the United States alone, while about 609,820 people will die of cancer. Finding new ways to treat this disease, which takes many shapes, is certainly a top priority for the world’s medical researchers.

Medication technology that delivers therapeutic drugs to cancer patients through implants has already been in existence. In general, nanotechnology has been among the most widely-researched new strategies in modern cancer research. Besides drug delivery, it has been used in gene therapy, cancer detection and diagnosis, biomarker mapping, targeted therapy, and molecular imaging, as outlined in this medical review. 

Certain nanomaterials have been developed, such as gold nanoparticles and quantum dots, with the purpose of improving cancer diagnosis at the molecular level, which would lead to more accurate and quicker detection of cancers. Other nanomaterials, like carbon nanotubes, polymeric micelles, or even T cells, have been put to work in cancer drug design, including as drug delivery agents. The use of these materials has led to significant pharmacokinetic and pharmacodynamic benefits both in cancer diagnosis and treatment.

Another use of nanotech has been in employing immunotherapeutic agents in order to slow down the speed with which cancer cells invade the body's tissues and help to boost the body's natural immune response. 

However, the researchers who conducted the medical review also note that "administering cancer immunotherapy in a safer, more controlled manner could extend the curative potential of these therapeutic agents to a broader range of patients and could also reduce toxicities."

What’s different about the technology in the new study is that while previously-developed nanotech has been used to fight cancers over relatively short durations, the device invented by the Houston Methodist team is meant to be used in a controlled fashion over a longer term. This is also what allows it to avoid many side effects.

Next for the researchers is additional testing to make sure the devices are safe. They are looking to make them available for patients within the next five years.

Insight from the researcher

Interesting Engineering (IE) reached out to Dr. Alessandro Grattoni, Ph.D., the study’s co-corresponding author and chair of the Department of Nanomedicine at Houston Methodist Research Institute, for more insight into the paper.

The following exchange has been lightly edited for clarity and flow.

Interesting Engineering: How does the device your team invented function? Is it pre-programmed to deliver treatment?

Dr. Grattoni: The implant uses a nanofluidic membrane microfabricated in Si-SiC with nanochannels as small as 10 nm to control the diffusive release of drug molecule from the drug reservoir into the body. The drug is loaded in the drug reservoir in a lyophilized form, and interstitial fluids from the body permeated through the membrane activate a steady solubilization/diffusion process where the release is controlled by the electrostatic interactions between drug molecules and the nanochannel walls. In that sense, the implant is pre-programmed based on nanochannel size and properties.

IE: What would be transformative about this approach in delivering cancer care?

It can activate the immune system locally, generating an anti-tumor response on site and systemic, without adverse effect to the patient. Notably, it reduces substantially the amount of drug needed for treatment, and therefore it could render treatment significantly more affordable.

IE: Could the device function in an ongoing fashion and treat chronic cancer patients their whole lives?  In principle, it could. However, it may require implant replacement, which would require a procedure similar to a biopsy collection under image guidance. IE: How soon would this technology be ready for testing on humans? 

We have formed a spin-off company (Semper Therapeutics) that is dedicated to taking this technology to patients. With the right funding support, this implant could reach first-in-human trials within two years.

Check out the study “Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer,” published in Advanced Science.

Study abstract

Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold-to-hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low-dose intratumoral delivery of CD40 mAb via the nanofluidic drug-eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment-related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment.