Researchers at NOVA Medical School have developed a hydrogel containing nanoparticles capable of transporting and controllably releasing two drugs used to treat pancreatic cancer. In an animal model, the new system significantly reduced tumor growth and spread compared to the same drugs in their free form.
The research, published in the American Chemical Society’s scientific journal ACS Nano Medicine, seeks to address one of the main challenges in treating pancreatic cancer: delivering sufficient amounts of the drugs to tumor cells, protecting them from degradation, and prolonging their action.
The system combines a hyaluronic acid-based hydrogel with nanoparticles that carry gemcitabine (GEM) and paclitaxel (PTX), two drugs used to treat the disease. Administered into the abdominal cavity via the intraperitoneal route, the hydrogel acts as a “safe,” protecting the nanoparticles and releasing them over an extended period. Once inside the cells, high levels of glutathione act as a sort of “opening code,” triggering the release of gemcitabine. Paclitaxel, in turn, is released gradually.
“It’s a new way to encapsulate two well-known anticancer drugs using smart nanomicelles embedded in a hydrogel, designed to promote drug release inside tumor cells and increase the amount of drug available to take effect,” explains João Conde, a researcher at NOVA Medical School and the study’s lead author.
In laboratory tests with pancreatic cancer cells, the drugs showed greater efficacy when administered via this system than in their free form: the concentration required to reduce the cells’ metabolic activity by 50% was 2.3 times lower for gemcitabine and 61.7 times lower for paclitaxel.
The system was then evaluated in an animal model of metastatic pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer. Compared to conventional formulations, the treatment significantly reduced tumor growth and the development of metastases. The combination of the hydrogel and nanoparticles also produced a prolonged antitumor response after a single administration.
The team also analyzed gene activity in tumor cells after treatment and observed changes in the PI3K-Akt and MAPK cellular signaling pathways, which are involved in the growth, survival, and proliferation of cancer cells.
These results suggest that, in addition to improving drug delivery, the system may also influence molecular mechanisms associated with disease progression and, in the future, contribute to the development of therapies tailored to the genomic characteristics of each tumor.
According to the authors, these results establish a preclinical foundation for continuing the development of the strategy, including additional studies on safety, pharmacokinetics, and validation in models that more closely mimic the human disease, prior to a potential clinical evaluation.
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Publication
Ravasco JMJM, Oliveira J, Conniot J, Mendes BB, Leal C, Fernandes SN, Afonso CAM, Conde J. In Vivo Multimodal Self-Immolative Prodrug Nanomicelle-Hydrogel Modulate Key Intratumoral and Metastatic Genomic Signaling Pathways in Pancreatic Cancer. ACS Nano Med. 2026 Jul 7;1(7):1640-1658. doi: 10.1021/acsnanomed.5c00174. PMID: 42639086; PMCID: PMC13501496.