Cancer cell membrane-derived nanoparticles improve the activity of gemcitabine and paclitaxel on pancreatic cancer cells and coordinate immunoregulatory properties on professional antigen-presenting cells

Abstract

Human pancreatic carcinoma is among the neoplasias with the highest number of deaths, and the frequency of relapses has demanded novel therapeutic intervention. Currently, the simultaneous application of different chemotherapeutics improves treatment efficiency in patients. However, the low specificity of these molecules may increase the cytotoxic side effects in healthy cells. Nanocarriers conjugated with aptamers and monoclonal antibodies target distinct proteins expressed on cancer cells and can be used to increase drug activity in disease sites. A recent advance in nanoengineering has led to the isolation of cell membrane lipids and proteins from cytoplasmatic organelles by ultracentrifugation, and the double-layer surface is used to coat organic and inorganic nanoparticles to prolong their permanence in the bloodstream. Additionally, plasmatic cell components form lipid nanovesicles that can deliver antineoplastic molecules. The present study aims to isolate the major components from pancreatic tumor cell membranes (PANC-1) to fabricate nanoparticles (MNPs) encapsulating two first-line drugs used in clinical treatment, viz., gemcitabine (GEM) and paclitaxel (PTX). Our results demonstrate that the MNP-GEM-PTX are very stable and induce greater cytotoxic effects on PANC-1 cells, in comparison to the use of pure GEM+PTX. The most interesting finding is that MNPs also interact with monocytes and dendritic cells, increasing the expression of costimulatory molecules CD80, CD83, CD86, and HLA-DR, indicating that the drug-carrier property of MNPs upregulates the activation of white blood cells. Therefore, a novel class of nanoparticles has been used to deliver antineoplastic agents to cancer cells and antigenic material to antigen-presenting cells. We also investigated their ability to modulate immune cells, aiming to promote pro-inflammatory responses in tumor sites.