title: Squalenoyl gemcitabine nanomedicine overcomes the low efficacy of gemcitabine therapy in pancreatic cancer.
abstract: Development of chemoresistance and rapid inactivation of gemcitabine (Gem), the standard therapy for advanced pancreatic cancer, are responsible of the major therapeutic failures. To overcome the above drawbacks we designed a novel nanomedicine strategy for Gem nanoparticle (NP) formulation based on squalene conjugation. The purpose was to investigate the antitumor efficacy of gemcitabine-squalene (SQ-Gem) NPs on chemoresistant and chemosensitive pancreatic adenocarcinoma models. Cell viability and apoptosis assays showed that SQ-Gem NPs displayed higher antiproliferative and cytotoxic effects, particularly in chemoresistant Panc1 tumor cells. In in vivo studies, compared to native Gem, SQ-Gem NPs decreased significantly the tumor growth, prevented tumor cell invasion, and prolonged the survival time of mice bearing orthotopic pancreatic tumors. These results correlate with a greater reduction of Ki-67 and induction of apoptosis. These findings demonstrate the feasibility of utilizing SQ-Gem NPs to make tumor cells more sensitive to Gem and thus provide an efficient new therapeutic alternative for pancreatic adenocarcinoma.
  
  
  BACKGROUND
  Pancreatic malignancies represent some of the most notoriously treatment resistant cancer varieties. This paper discusses a novel and promising nanotechnology-based treatment approach, currently at the basic science stage.
authors.affiliation: University of Louis Pasteur-Strasbourg, France.
authors.forename: Soukaina
authors.initials: S
authors.lastname: Réjiba
authors.forename: L Harivardhan
authors.initials: LH
authors.lastname: Reddy
authors.forename: Christelle
authors.initials: C
authors.lastname: Bigand
authors.forename: Céline
authors.initials: C
authors.lastname: Parmentier
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Amor
authors.initials: A
authors.lastname: Hajri
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013185:Squalene / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D013185:Squalene; D000093542:Gemcitabine