title: Efficient "green" encapsulation of a highly hydrophilic anticancer drug in metal-organic framework nanoparticles.
abstract: Metal-organic frameworks (MOFs) are coordination polymers of interest for biomedical applications. Of particular importance, nanoparticles made of iron(III) trimesate (MIL-100, MIL standing for Material Institut Lavoisier) (nanoMOFs) can be conveniently synthesised under mild and green conditions. They were shown to be biodegradable, biocompatible and efficient to encapsulate a variety of active molecules. We have addressed here the challenges to encapsulate a highly hydrophilic anticancer prodrug, phosphated gemcitabin (Gem-MP) known for its instability and inability to bypass cell membranes. MIL-100 nanoMOFs acted as efficient "nanosponges", soaking Gem-MP from its aqueous solution with almost perfect efficiency (>98%). Maximal loadings reached ∼30 wt% reflecting the strong interaction between the drug and the iron trimesate matrices. Neither degradation nor loss of crystalline structure was observed after the loading process. Storage of the loaded nanoMOFs in water did not result in drug release over three days. However, Gem-MP was released in media containing phosphates, as a consequence to particle degradation. Drug-loaded nanoMOFs were effective against pancreatic PANC-1 cells, in contrast to free drug and empty nanoMOFs. However, an efflux phenomenon could contribute to reduce the efficacy of the nanocarriers. Size optimization and surface modification of the nanoMOFs are expected to further improve these findings.
authors.affiliation: a Institut Galien (UMR CNRS 8612), Université Paris-Sud , Châtenay-Malabry , France .
authors.forename: Violeta
authors.initials: V
authors.lastname: Rodriguez-Ruiz
authors.affiliation: a Institut Galien (UMR CNRS 8612), Université Paris-Sud , Châtenay-Malabry , France .
authors.forename: Andrei
authors.initials: A
authors.lastname: Maksimenko
authors.affiliation: b National Centre for Scientific Research "Demokritos", Institute of Nanoscience & Nanotechnology , Ag. Paraskevi , Athens , Greece , and.
authors.forename: Resmi
authors.initials: R
authors.lastname: Anand
authors.affiliation: c Istituto per la Sintesi Organica e la Fotoreattività-CNR , Bologna , Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Monti
authors.affiliation: a Institut Galien (UMR CNRS 8612), Université Paris-Sud , Châtenay-Malabry , France .
authors.forename: Valentina
authors.initials: V
authors.lastname: Agostoni
authors.affiliation: a Institut Galien (UMR CNRS 8612), Université Paris-Sud , Châtenay-Malabry , France .
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.affiliation: b National Centre for Scientific Research "Demokritos", Institute of Nanoscience & Nanotechnology , Ag. Paraskevi , Athens , Greece , and.
authors.forename: Maria
authors.initials: M
authors.lastname: Lampropoulou
authors.affiliation: b National Centre for Scientific Research "Demokritos", Institute of Nanoscience & Nanotechnology , Ag. Paraskevi , Athens , Greece , and.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Yannakopoulou
authors.affiliation: a Institut Galien (UMR CNRS 8612), Université Paris-Sud , Châtenay-Malabry , France .
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003460:Crystallization; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053768:Metal Nanoparticles; D009942:Organometallic Compounds / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010710:Phosphates / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005290:Ferric Compounds; D009942:Organometallic Compounds; D010710:Phosphates; D011108:Polymers; D011355:Prodrugs; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabin; MOF; metal–organic frameworks; nanoparticle; nucleoside analog; prostate cancer; “green” synthesis