MMP2-activated bioadhesive MAP nanoparticles enhance gemcitabine delivery, suppressing pancreatic tumor growth.

Pancreatic cancer (PDAC) remains a highly lethal malignancy, primarily due to late diagnosis and the limited effectiveness of conventional systemic chemotherapy. The dense fibrotic stroma and aberrant tumor vasculature characteristic of PDAC create significant barriers, impeding drug penetration and accumulation within the tumor microenvironment. This often leads to suboptimal drug concentrations at the tumor site and severe systemic side effects, highlighting an urgent need for targeted drug delivery strategies that can overcome these challenges and improve therapeutic outcomes.

Researchers developed bioengineered mussel adhesive protein (MAP)-derived nanoparticles, shielded with polyethylene glycol (PEG) via a matrix metalloproteinase-2 (MMP2)-cleavable peptide linker. These Gemcitabine-loaded shielded MAP nanoparticles (Gem-S-MNPs) were evaluated for drug encapsulation efficiency and enzyme-mediated PEG deshielding in vitro. Their anticancer efficacy was compared to free gemcitabine against pancreatic cancer cells. In vivo, Gem-S-MNPs were administered intravenously to assess intratumoral accumulation, retention, tumor growth suppression, and systemic toxicity, with histological analyses confirming treatment effects.