Innovative Mussel Protein Nanotechnology Delivers Drugs Directly to Pancreatic Tumors

Pancreatic cancer is considered one of the most lethal cancer because it is often diagnosed late and is difficult to treat. However, a South Korean research team has recently succeeded in developing "smart nanoparticles" that remain hidden in normal tissue but shed their protective coating and release anticancer drugs once they reach tumor tissue. This drug delivery technology is attracting attention for its potential to reduce the side effects of cancer treatment while significantly improving treatment efficacy.

The findings of this study, conducted by a research team headed by Professor Hyung Joon Cha of the Department of Chemical Engineering and the Graduate School of Convergence Science and Technology at POSTECH (Pohang University of Science and Technology), together with Ph.D. candidate Hyeokjun Lee of the Department of Chemical Engineering, were recently published in the online edition of Biomaterials, an international academic journal in the field of biomaterials.

Pancreatic cancer is a notoriously difficult-to-treat disease because it is located deep within the body, making it hard to detect in its early stages, and it spreads rapidly to surrounding organs. While intravenous chemotherapy is the most widely used treatment, "gemcitabine"-a leading drug in this class-breaks down rapidly in the bloodstream and fails to reach the tumor tissue in sufficient quantities. Furthermore, it has the limitation of also attacking normal cells, causing severe systemic side effects.

To address this issue, the research team drew inspiration from the principle that allows mussels to cling firmly even to wet rocks. Using molecular synthetic biotechnology, they mass-produced "mussel adhesive protein," converted it into nanoparticles, encapsulated gemcitabine inside them, and coated the surface with a protective layer of the biocompatible polymer "polyethylene glycol (PEG)." Thanks to this protective layer, the nanoparticles can conceal their adhesive properties while traveling through the bloodstream, evading attacks from immune cells and circulating stably throughout the body.

The key to this study is a "spatially controlled stimulus-response system" designed so that the protective coating is removed only in tumor tissue. The research team used a special peptide-which is cleaved only by "MMP2," an enzyme secreted in particularly high amounts in pancreatic cancer tissue-as the link in the protective coating. As a result, the nanoparticles retain their protective coating while in the bloodstream, but once they reach tumor tissue, the coating is removed by the MMP2 enzyme. Once stripped of their protective coating, these "stealth" nanoparticles regain the strong adhesive properties of mussel adhesive protein, firmly attaching themselves to the tumor tissue. They then penetrate the cancer cells and continuously release the anticancer drug, selectively attacking only the cancer cells.

When these nanoparticles were administered intravenously in an animal model of pancreatic cancer, the results were striking. Compared to cases where conventional anticancer drugs were administered alone or where standard nanoparticles were used, the accumulation and retention time of the nanoparticles within the tumor tissue increased by more than 60%. No systemic toxicity was observed, and tumor volume and weight were reduced by more than half compared to the group treated with conventional anticancer drugs alone. Histological analysis also confirmed widespread cancer cell death.

This technology is significant because it not only enhances treatment efficacy by keeping the drug in the tumor tissue for a longer period but also reduces the amount of drug delivered to normal tissue, thereby minimizing systemic side effects-a major challenge in cancer treatment. The research team plans to further develop this platform into a next-generation targeted drug delivery technology that can be applied not only to pancreatic cancer but also to the treatment of various intractable solid tumors where drug delivery is difficult.

The drug delivery platform we have developed is a novel systemic treatment that, even when administered intravenously, is selectively activated only within tumor tissue to release the drug. By reducing the side effects of cancer treatment while enhancing its efficacy, it will offer hope to patients with intractable solid tumors, including pancreatic cancer."

Hyung Joon Cha, Professor, Department of Chemical Engineering, POSTECH (Pohang University of Science and Technology) 

Meanwhile, this research was conducted with support from the National Research Laboratories (NRL) 2.0 program of the National Research Foundation of Korea (NRF) under the Ministry of Science and ICT, and the Support Program for Promoting the Dissemination of Outstanding R&D Achievements by the Commercializations Promotion Agency for R&D Outcomes (COMPA).