Dual Drug Loaded Nanotheranostic Platforms as a Novel Synergistic Approach to Improve Pancreatic Cancer Treatment

Abstract

This study focuses on the development of theranostic, dual drug-loaded nanocarriers to propose a proof-of-principle therapeutic approach in the treatment of pancreatic ductal adenocarcinoma (PDAC). The nanoconstructs consist of a core of zinc oxide nanocrystals doped with gadolinium, useful as a potential contrast agent in magnetic resonance imaging applications. After functionalizing their surface with amino-propyl groups, the physical adsorption of two hydrophobic drugs is performed: Vismodegib and Sorafenib. Their synergistic use might improve PDAC treatment and stroma depletion when co-delivered in the tumor microenvironment for future in vivo applications. To enhance the nanoconstructs’ biostability, the ensemble is coated by a lipid bilayer and a tumor targeting peptide is incorporated on the outer shell surface. As a first proof of concept, the resulting nanoconstructs are tested against two pancreatic cancer cell lines, showing a modest increase in treatment efficacy compared to the free drug counterparts and proving to spare healthy pancreatic cells. In a second testing set, the dual-drug loaded nanoconstructs are tested on both cell lines previously sensitized to a first-line chemotherapeutic drug, Gemcitabine, showing an improved treatment response. From these preliminary results, the nanotheranostic platforms might constitute a good starting point for future PDAC therapy and diagnosis studies.