Researchers at the University of Arizona have unveiled a groundbreaking method to enhance the delivery of chemotherapy drugs to pancreatic and breast cancer tumors, reducing collateral damage to healthy tissues. This innovative approach, detailed in a paper published today in Nature Cancer, could revolutionize cancer treatment by overcoming the limitations of traditional chemotherapy.
The new formulation of the drug paclitaxel, developed by the research team, promises to improve drug delivery and minimize side effects, potentially setting a new standard for cancer therapies. “Paclitaxel is potent and kills cancer cells, but to unleash its full therapeutic potential, we have to address its toxicity,” explained Jianqin Lu, PhD, an endowed associate professor at the University of Arizona’s R. Ken Coit College of Pharmacy and a member of the Comprehensive Cancer Center. “That means finding a better way to get it to tumor cells while also making it stay around longer.”
Revolutionizing Chemotherapy with Nanotechnology
Paclitaxel has long been a staple in cancer chemotherapy, treating a variety of cancers such as breast, pancreatic, lung, and ovarian. However, its efficacy is often hindered by its tendency to affect healthy tissues, including the liver and spleen. The new delivery method leverages the unique properties of tiny, fatty bubbles known as nanovesicles. These nanovesicles, a type of nanoparticle, are engineered to improve drug delivery by chemically attaching paclitaxel to sphingomyelin, a fat found in cell membranes.
“Such structures enable the drug to have better tumor delivery and stay in circulation longer, accumulating in the tumor site and less so in healthy tissue,” Lu noted. The new formulation, dubbed Paclitaxome, has demonstrated superior performance compared to existing chemotherapy drugs Taxol and Abraxane in preclinical tests on mice with triple-negative breast cancer and advanced pancreatic cancer.
Clinical Promise and Future Applications
The research team further enhanced the formulation, creating an improved version known as CD47p/AZE-Paclitaxome, which resulted in reduced tumor growth and prolonged survival in animal models. “Many chemotherapy drugs have poor delivery,” remarked study co-author and oncologist Aaron Scott, MD, an associate professor of medicine at the University of Arizona College of Medicine – Tucson. “Paclitaxome is clinically promising because the system delivers the drug at the tumor site and will prevent side effects. The drug isn’t cleared from the system as quickly. All of this improves its efficacy.”
The modified paclitaxel also facilitated the effective delivery of drug combinations. The researchers successfully tested a combination of paclitaxel and gemcitabine by incorporating gemcitabine into the nanovesicle core. “We screened different drug ratios and then loaded the best one into the nanovesicle,” said Lu. “The combination outperformed the co-administration of gemcitabine plus Taxol as well as the combination of Abraxane and gemcitabine.”
Expanding the Horizons of Cancer Treatment
In another experiment, the team combined the modified paclitaxel with carboplatin to prevent recurrence of triple-negative breast cancer in mice while eliminating metastases. “This strategy can be applied to other drugs and also other diseases,” Lu stated. “We applied this nanovesicle strategy to another chemotherapy drug, camptothecin, and it worked well in a colon cancer mouse model. That demonstrated the generalizability of this technology to an array of drugs.”
Looking ahead, Lu envisions using this approach to deliver chemotherapy drugs in tandem with immunotherapies, aiming to harness the immune system against cancer. The team is actively gathering more preclinical data to further understand the platform’s applications. “Our goal is to take this into first-in-human clinical trials,” Scott added. “This platform can span a variety of tumor types for patients who desperately need better therapies.”
The study’s co-authors include Zhiren Wang, PhD, now a professor at the South China University of Technology, and several researchers and students from the University of Arizona. The research was supported by the National Institute of General Medical Sciences and the National Cancer Institute, both divisions of the National Institutes of Health.
