Premium
Towards an Improved anti‐HIV Activity of NRTI via Metal–Organic Frameworks Nanoparticles
Author(s) -
Agostoni Valentina,
Chalati Tamim,
Horcajada Patricia,
Willaime Hervé,
Anand Resmi,
Semiramoth Nicolas,
Baati Tarek,
Hall Shaun,
Maurin Guillaume,
Chacun Hélène,
Bouchemal Kawthar,
Martineau Charlotte,
Taulelle Francis,
Couvreur Patrick,
RogezKreuz Christine,
Clayette Pascal,
Monti Sandra,
Serre Christian,
Gref Ruxandra
Publication year - 2013
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201200454
Subject(s) - biocompatibility , isothermal titration calorimetry , metal organic framework , drug delivery , supramolecular chemistry , materials science , titration , nanoparticle , human immunodeficiency virus (hiv) , combinatorial chemistry , nanotechnology , drug , chemical engineering , biodegradation , chemistry , molecule , organic chemistry , biochemistry , pharmacology , metallurgy , medicine , family medicine , adsorption , engineering
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.