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Targeted Nanoparticles for the Delivery of Novel Bioactive Molecules to Pancreatic Cancer Cells

Uncategorized

May 312016

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.

Targeted Nanoparticles for the Delivery of Novel Bioactive Molecules to Pancreatic Cancer Cells

Vanna Sanna^†^||, Salvatore Nurra^†, Nicolino Pala^†, Salvatore Marceddu^§, Divya Pathania^⊥, Nouri Neamati^*^‡, andMario Sechi^*^†^||

^† Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy

^|| Laboratory of Nanomedicine, University of Sassari, c/c Porto Conte Ricerche, 07041 Alghero, Italy

^§Istituto di Scienze delle Produzioni Alimentari (ISPA)-CNR, sez. di Sassari, 07040 Baldinca, Italy

^⊥ Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, California 90089, United States

^‡ Department of Medicinal Chemistry, College of Pharmacy, Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, United States

J. Med. Chem., Article ASAP

DOI: 10.1021/acs.jmedchem.5b01571

*Phone: +1 734 647-2732. E-mail: neamati@umich.edu. Fax: +1 734 647-8430., *Phone: +39 079-228-753. E-mail:mario.sechi@uniss.it. Fax: +39 079-229-559.

http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01571

////////Targeted Nanoparticles, Delivery, Novel Bioactive Molecules, Pancreatic Cancer Cells