title: Towards an improved anti-HIV activity of NRTI via metal-organic frameworks nanoparticles.
abstract: Nanoscale mesoporous iron carboxylates metal-organic frameworks (nanoMOFs) have recently emerged as promising platforms for drug delivery, showing biodegradability, biocompatibility and important loading capability of challenging highly water-soluble drugs such as azidothymidine tryphosphate (AZT-TP). In this study, nanoMOFs made of iron trimesate (MIL-100) were able to act as efficient molecular sponges, quickly adsorbing up to 24 wt% AZT-TP with entrapment efficiencies close to 100%, without perturbation of the supramolecular crystalline organization. These data are in agreement with molecular modelling predictions, indicating maximal loadings of 33 wt% and preferential location of the drug in the large cages. Spectrophotometry, isothermal titration calorimetry, and solid state NMR investigations enable to gain insight on the mechanism of interaction of AZT and AZT-TP with the nanoMOFs, pointing out the crucial role of phosphates strongly coordinating with the unsaturated iron(III) sites. Finally, contrarily to the free AZT-TP, the loaded nanoparticles efficiently penetrate and release their cargo of active triphosphorylated AZT inside major HIV target cells, efficiently protecting against HIV infection.
authors.affiliation: Institut Galien, UMR 8612 CNRS Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Agostoni
authors.forename: Tamim
authors.initials: T
authors.lastname: Chalati
authors.forename: Patricia
authors.initials: P
authors.lastname: Horcajada
authors.forename: Hervé
authors.initials: H
authors.lastname: Willaime
authors.forename: Resmi
authors.initials: R
authors.lastname: Anand
authors.forename: Nicolas
authors.initials: N
authors.lastname: Semiramoth
authors.forename: Tarek
authors.initials: T
authors.lastname: Baati
authors.forename: Shaun
authors.initials: S
authors.lastname: Hall
authors.forename: Guillaume
authors.initials: G
authors.lastname: Maurin
authors.forename: Hélène
authors.initials: H
authors.lastname: Chacun
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martineau
authors.forename: Francis
authors.initials: F
authors.lastname: Taulelle
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Christine
authors.initials: C
authors.lastname: Rogez-Kreuz
authors.forename: Pascal
authors.initials: P
authors.lastname: Clayette
authors.forename: Sandra
authors.initials: S
authors.lastname: Monti
authors.forename: Christian
authors.initials: C
authors.lastname: Serre
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002478:Cells, Cultured; D054306:Dideoxynucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry*; D013942:Thymine Nucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D015215:Zidovudine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D044966:Anti-Retroviral Agents; D054306:Dideoxynucleotides; D005290:Ferric Compounds; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate
keywords: AZT-TP; NRTI; drug delivery; metal organic framework; nanoparticle