Plasma Protein Corona Fingerprinting Across Intraductal Papillary Mucinous Neoplasms and Pancreatic Ductal Adenocarcinoma: A Comparative Proof-of-Concept Study

Background/Objectives: Surveillance of intraductal papillary mucinous neoplasms (IPMNs) provides a clinically relevant window in which biological changes associated with pancreatic ductal adenocarcinoma (PDAC) development may potentially be investigated before advanced disease occurs. Nanoparticle-enabled protein corona (PC) fingerprinting has shown analytical potential in PDAC, but the extent to which different nanoplatforms recover distinct information across the biologically proximate IPMN-PDAC spectrum remains unclear. This exploratory study compared three nanoplatform configurations to identify a candidate workflow for subsequent validation. Methods: Plasma from 22 patients with de novo PDAC (n = 11), IPMN (n = 6), or IPMN-derived PDAC (n = 5) was incubated with graphene oxide (GO) nanosheets, gold nanoparticles (AuNPs), or cationic DOTAP-DOPE liposomes. Wash-resistant PCs were analyzed by SDS-PAGE, quantified across predefined molecular weight (MW) regions, and evaluated using exploratory linear discriminant analysis with repeated stratified cross-validation. Results: The three nanoplatforms generated non-equivalent electrophoretic PC architectures. In this small exploratory cohort, GO showed the broadest pattern of nominal clinical-group-associated variation in relative MW-region contributions and yielded internal cross-validation AUC estimates of 0.955 for IPMN versus de novo PDAC, 0.767 for IPMN versus IPMN-derived PDAC, and 0.927 for IPMN-derived versus de novo PDAC. Corresponding AUCs were 0.606–0.700 for AuNPs and 0.621–0.691 for liposomes. Conclusions: GO provided the broadest group-associated variation and numerically highest internal discrimination estimates, supporting its prioritization for independent validation and prospective longitudinal evaluation in IPMN surveillance.