Targeted Nanoparticles for the Delivery of Novel Bioactive Molecules to Pancreatic Cancer Cells
Vanna Sanna1,2, Salvatore Nurra1, Nicolino Pala1
1Department of Chemistry and Pharmacy, University of Sassari , 07100 Sassari, Italy.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis and limited therapeutic options. Therefore, there is an urgent need to identify new, safe, and targeted therapeutics for effective treatment of late as well as early stage disease. Plectin-1 (Plec-1) was recently identified as specific biomarker for detecting PDAC at an early stage. We envisioned that multivalent attachment of nanocarriers incorporating certain drugs to Plec-1-derived peptide would increase specific binding affinity and impart high specificity for PDAC cells. Previously, we discovered a novel class of compounds (e.g., quinazolinediones, QDs) that exert their cytotoxic effects by modulating ROS-mediated cell signaling. Herein, we prepared novel QD242-encapsulated polymeric nanoparticles (NPs) functionalized with a peptide to selectively bind to Plec-1. Similarly, we prepared QD-based NPs densely decorated with an isatoic anhydride derivative. Furthermore, we evaluated their impact on ligand binding and antiproliferative activity against PDAC cells. The targeted NPs were more potent than the nontargeted constructs in PDAC cells warranting further development.
Insights
New targeted nanoparticles show promise for treating pancreatic cancer. These nanoparticles, functionalized with a peptide targeting Plectin-1 (Plec-1), demonstrated enhanced potency against pancreatic ductal adenocarcinoma (PDAC) cells.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options.
- Plectin-1 (Plec-1) is a newly identified biomarker for early PDAC detection.
- Novel quinazolinedione (QD) compounds exhibit cytotoxicity by modulating ROS-mediated cell signaling.
Purpose of the Study:
- To develop targeted nanocarriers for enhanced PDAC treatment.
- To investigate the efficacy of Plec-1-targeted nanoparticles loaded with QD242.
- To assess the impact of peptide functionalization on nanoparticle binding and antiproliferative activity.
Main Methods:
- Preparation of QD242-encapsulated polymeric nanoparticles (NPs) functionalized with a Plec-1-targeting peptide.
- Synthesis of QD-based NPs decorated with an isatoic anhydride derivative.
- Evaluation of ligand binding and antiproliferative effects of targeted NPs on PDAC cells.
Main Results:
- Targeted NPs exhibited increased specificity and binding affinity for PDAC cells.
- QD242-loaded NPs functionalized with Plec-1 peptide demonstrated enhanced potency against PDAC cells compared to non-targeted NPs.
- QD-based NPs with isatoic anhydride derivative also showed promising activity.
Conclusions:
- Peptide-functionalized nanoparticles represent a promising targeted therapeutic strategy for PDAC.
- The developed targeted NPs show potential for improved treatment of both early and late-stage PDAC.
- Further development of these targeted nanotherapeutics is warranted for clinical application.
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