Advanced Nanoparticle Platform for Targeted Pancreatic Cancer Therapy: Optimized Gemcitabine Delivery with Biomimetic Coatings

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its late diagnosis, aggressive invasiveness, and limited responsiveness to conventional therapies. Although gemcitabine remains a first-line chemotherapeutic agent, its clinical efficacy is hindered by rapid systemic clearance, poor cellular uptake, and the emergence of drug resistance. In this study, we present a biomimetic nanotherapeutic platform, Fullgem, composed of gemcitabine-loaded fullerene nanoparticles cloaked with PANC-1 pancreatic cancer cell membranes. Fullerenes were selected as a core material owing to their favorable physicochemical properties, including high surface area, architectural versatility, biocompatibility, and superior stability, which facilitate effective drug loading and delivery. The homologous membrane coating not only stabilizes the nanoparticles but also enhances tumor-targeting specificity and cellular uptake while mitigating off-target cytotoxicity. Notably, recent findings indicate that such membrane-coated fullerenes can self-assemble into ordered, flower-like nanostructures, potentially improving biodistribution. In vitro assays demonstrated that Fullgem significantly increased intracellular gemcitabine accumulation in PANC-1 cells within one hour and markedly reduced toxicity in non-malignant cells. Furthermore, the membrane-coating strategy effectively addressed pharmacokinetic limitations, including short half-life and chemoresistance. These findings underscore the potential of Fullgem as a promising nanoplatform for precision delivery of chemotherapeutics in treatment-refractory pancreatic cancer.