Biocompatible nanoparticles

… to enhance systemic delivery of cancer immunotherapy.

PLGA nanoparticles modified with ATP slowly release anti-cancer drugs and recruit immune cells to fight tumors.

Purdue University researchers are developing and validating patent-pending poly (lactic-co-glycolic acid), or PLGA, nanoparticles modified with adenosine triphosphate, or ATP, to enhance immunotherapy effects against malignant tumors.

The nanoparticles slowly release drugs that induce immunogenic cell death, or ICD, in tumors. ICD generates tumor antigens and other molecules to bring immune cells to a tumor’s microenvironment. The researchers have attached ATP to the nanoparticles, which also recruits immune cells to the tumor to initiate anti-tumor immune responses.

Yoon Yeo leads a team of researchers from the College of Pharmacy, the Metabolite Profiling Facility in the Bindley Bioscience Center, and the Purdue Institute for Cancer Research to develop the nanoparticles. Yeo is the associate department head and Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics and Biomedical Engineering; she is also a member of the Purdue Institute for Drug Discovery and the Purdue Institute for Cancer Research.

The researchers validated their work using paclitaxel, a chemotherapy drug used to treat several types of cancers. They found that tumors grew slower in mice treated with paclitaxel enclosed within ATP-modified nanoparticles than in mice treated with paclitaxel in non-modified nanoparticles.

“When combined with an existing immunotherapy drug, the ATP-modified, paclitaxel-loaded nanoparticles eliminated tumors in mice and protected them from rechallenge with tumor cells,” Yeo said.

The research has been published in the peer-reviewed journal ACS Nano.

Challenges to systemic immunotherapy delivery

Immunotherapy is a promising approach to fighting cancer, but Yeo said it does not benefit a large population of patients because they do not have the powerful immune cells needed to combat tumors.

“Pharmacological agents to activate immune cells can directly be given to tumors,” Yeo said. “Then the immune system can fight not only the treated tumors but also nontreated tumors in distant locations as the activated immune cells circulate in the bloodstream.”

However, Yeo said most tumors with poor prognoses are not always locatable or accessible. Therefore, they may not be effectively treated by local therapy. She and her team envisioned systemic delivery of immunotherapy, but there are challenges.

“For successful systemic administration, active ingredients that stimulate anti-tumor immune responses need to be simultaneously present in tumors to exert concerted effects on the target,” Yeo said. “The ingredients also must maintain their activity until they reach tumors, but not cause toxic off-target effects. Moreover, the carriers traditionally used in local drug delivery offer limited utility in systemic application because they may not be compatible with blood components.”

Yeo and her colleagues used biocompatible polymeric nanoparticles to deliver immunotherapy compounds and modified them to safely activate the immune system.

“We employed poly (lactic-co-glycolic acid), or PLGA, nanoparticles based on the strong track record of the polymer in FDA-approved products and its routine use in the systemic delivery of poorly water-soluble drugs,” Yeo said.

Tests verified the ATP-modified PLGA nanoparticles were well tolerated in mice upon multiple systemic injections. They were able to recruit dendritic cells, the immune cells that recognize tumor antigens and bring specialized immune cells to fight off tumors.

“Moreover, the nanoparticles were shown to control the release of paclitaxel to minimize its systemic toxicity,” Yeo said.

The next development steps

Yeo and her colleagues will continue their work on the ATP-modified nanoparticles.

“We are currently working on improving the delivery of the nanoparticles to tumors and combining them with other treatments that will circumvent the resistance to the nanoparticle-delivered immunotherapy,” Yeo said. “To finance these efforts, we will apply for continued support from the National Institutes of Health. We are also open to industry partnerships to take this technology to the clinic.”

Yeo disclosed the nanoparticles innovation to the Purdue Innovates Office of Technology Commercialization, which has applied for a patent from the U.S. Patent and Trademark Office to protect the intellectual property. Industry partners interested in developing the compound or commercializing it for the marketplace should contact Joe Kasper, assistant director of business development and licensing — life sciences, at jrkasper@prf.org, about track code 69546.

Yeo and the research team received funding from the National Institutes of Health, the National Center for Advancing Translational Sciences, the Indiana Clinical and Translational Sciences Institute, and the Purdue Institute for Cancer Research.

About Purdue University

Purdue University is a public research institution demonstrating excellence at scale. Ranked among top 10 public universities and with two colleges in the top four in the United States, Purdue discovers and disseminates knowledge with a quality and at a scale second to none. More than 105,000 students study at Purdue across modalities and locations, including nearly 50,000 in person on the West Lafayette campus. Committed to affordability and accessibility, Purdue’s main campus has frozen tuition 13 years in a row. See how Purdue never stops in the persistent pursuit of the next giant leap — including its first comprehensive urban campus in Indianapolis, the new Mitchell E. Daniels, Jr. School of Business, and Purdue Computes — at https://www.purdue.edu/president/strategic-initiatives.

About Purdue Innovates Office of Technology Commercialization

The Purdue Innovates Office of Technology Commercialization operates one of the most comprehensive technology transfer programs among leading research universities in the U.S. Services provided by this office support the economic development initiatives of Purdue University and benefit the university’s academic activities through commercializing, licensing and protecting Purdue intellectual property. In fiscal year 2023, the office reported 150 deals finalized with 203 technologies signed, 400 disclosures received and 218 issued U.S. patents. The office is managed by the Purdue Research Foundation, which received the 2019 Innovation & Economic Prosperity Universities Award for Place from the Association of Public and Land-grant Universities. In 2020, IPWatchdog Institute ranked Purdue third nationally in startup creation and in the top 20 for patents. The Purdue Research Foundation is a private, nonprofit foundation created to advance the mission of Purdue University. Contact otcip@prf.org for more information.

Writer/Media contact: Steve Martin, sgmartin@prf.org

Source: Yoon Yeo, yyeo@purdue.edu

Journal: ACS Nano
DOI: 10.1021/acsnano.3c11445
Article Title: Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors
Article Publication Date: 16-Jan-2024