title: Targeted Nanoparticles for the Delivery of Novel Bioactive Molecules to Pancreatic Cancer Cells.
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.
authors.affiliation: 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.
authors.forename: Vanna
authors.initials: V
authors.lastname: Sanna
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari , 07100 Sassari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Nurra
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari , 07100 Sassari, Italy.
authors.forename: Nicolino
authors.initials: N
authors.lastname: Pala
authors.affiliation: Istituto di Scienze delle Produzioni Alimentari (ISPA)-CNR , sez. di Sassari, 07040 Baldinca, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Marceddu
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy , Los Angeles, California 90089, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Pathania
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, Translational Oncology Program, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.affiliation: 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.
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C000619631:QD242 compound; D052999:Quinazolinones