Jessai Flores, Illustrations Editor

Researchers from Yale University and the University of Connecticut published a paper in Science Advances on Feb. 8 focused on developing a nanoparticle-based treatment to combat glioblastomas, a type of brain cancer with poor survival and high recurrence rates in patients.

Precision medicine, a form of personalized treatment for cancers and other diseases, is rapidly developing to address cancer — the nanoparticle-based target tested in this research serves as a perfect example of such therapeutics. Nanoparticle-based targeted therapies demonstrate an ability to efficiently treat patients with cancer. Emerging therapies like these can pave the way to a move away from traditional chemo and radiation therapies.

According to the paper, researchers developed nanoparticle-based therapies that can specifically target overexpressed RNA molecules, known as “oncomiRs,” that promote cancer cell proliferation and tumor growth. By targeting areas of cancerous activity, these nanoparticles can inhibit the tumor-promoting activity of oncomiRs, potentially leading to improved cancer treatment outcomes. RNA plays a significant role in gene expression in all cells, including cancerous cells — however, cancer cells often present altered RNA expressions, which can contribute to cancer development and progression.

“We’ve taken the idea of a slow release polymer that can slowly release chemotherapy agents in the brain and we’ve shrunk it down so that you can introduce it into the brain through a tiny catheter that a neurosurgeon would place there,” said W. Mark Saltzman, professor of biomedical engineering at Yale. “These are nanoparticles that get infused in solution, right into the space where the tumor is.”

Saltzman has taught at Yale for 20 years and is the leader of the Saltzman Research Group. His research team is engaged in several endeavors to improve the safety and efficacy of medical and surgical treatment. Through his research lab on campus, he and his colleagues are developing mechanisms for directly delivering medicines to brain tumors, amongst others ailments. 

A key feature of nanoparticle-based treatments is the possibility of avoiding surgery, radiation therapy and other forms of cancer treatment that may negatively affect a patient. This approach enables the treatment of cancer by locally administering the medication, while those who take chemotherapy pills or receive chemotherapy injections may experience adverse effects in other parts of their bodies. In certain circumstances, pharmacological treatments may not reach the brain or the intended site.

“This idea of local therapy is one that has gained traction more quickly in treating brain tumors just because of their unique position in the body,” Saltzman said. “But I’ve also been working on other projects with other collaborators where we’re using the same concepts to treat ovarian cancer or skin cancer, and I think it can be applied more broadly to cancers as well.”

Saltzman noted that the advances in novel and innovative approaches to treating cancer are accompanied by a range of technical obstacles that are then resolved over time, step by step. Attempting to embed therapeutic molecules into a wafer the size of a dime presents difficulties, as does developing chemicals and biological agents that can target the RNA of cancerous cells. In addition, Saltzman highlighted the importance of using sophisticated models for drug trials to evaluate the efficacy and validity of possible cancer therapies.

This research paper highlights a significant milestone and achievement in treating glioblastoma, the result of continued work between chemists, pharmacists, neuro-oncologists and surgeons, and many others collaborating in developing practical and successful therapies. 

“It really requires a network of people, so me and the people in my lab, we’re good at this sort of early-stage research and engineering like what is described in the paper,” Saltzman emphasized.

Yazhe Wang, first author of the paper and former postdoctoral associate in the Saltzman lab, talked about her involvement in this research, specifically in assembling the delivery system for these therapeutics. A critical component of this therapy is delivering peptide nucleic acids, or PNA, effectively to the cancer site. This mechanism is essential to adequately treating glioblastoma. 

“We form a particle that can deliver our drug, or in this case PNA, to brain tumor cells,” Wang said. “When we deliver our system to an animal model with a great tumor, we found our system can shrink the tumor and prolong the animal’s survival time.”

The results of these research findings are promising, as Wang noted that the team observed a complete removal of the tumor in some animal cases. This conclusion suggests that the method may be a viable option for those looking for alternative solutions to cancer treatment, as the technique is practical, safe and easy to administer. 

“We have different projects, studies that are focusing on building up a nanoparticle like this delivery system,” said Wang. “You can use this delivery system for different purposes of therapeutic therapies. And in our case, I think the normal detail here is that we actually use a low code delivery method so we can inject our particles directly to the brain tumor.” 

In most cases of injection of medicine or treatments, only a small amount of the drug can get through the blood-brain barrier and reach the brain tumor cells. Wang highlighted how this research uses a local delivery method to get around this barrier and inject the medicine or nanoparticles directly into the brain. 

Raman Bahal, an associate professor of pharmaceutics at the University of Connecticut, developed the research PNA. As these molecules interact directly with RNAs that contribute to the malignant activity of the cell, the chemistry of nucleic acids is an essential aspect of treating glioblastomas. Bahal developed the biological and chemical strategies to target overexpressed or upregulated RNAs in cancer and block them from functioning, while Saltzman and Wang focused on medication delivery.

“Brain cancer is such a complicated problem that here we found that there are a few other biomarkers which are responsible, considering the malignancy of brain cancer,” Bahal said. “Here, we did not just kind of make some random molecule. In fact, we designed some molecules that target those bad genes in an effective way.”

Bahal used a missile analogy to describe the mechanisms in which molecules developed by his team collaborate with the delivery system to target cancer directly. He said that these molecules, coupled with an adequate delivery mechanism, are the driving force behind the promising results of this research paper.

In this era of precision medicine, Bahal highlighted numerous sequencing techniques that have proved their efficacy as therapeutics. Utilizing emerging technologies to address these problems is imperative, as the current status of cancer treatment has multiple undesirable side effects and outcomes. Bahal is enthusiastic about employing chemistry and biology to continue work on cancer treatment and improve outcomes. 

The recently published paper can be found in the Science Advances journal linked here.