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Porous nanoparticles with engineered shells release their drug cargo in cancer cells

[Display omitted] Highly porous nanoscale metal–organic frameworks (nanoMOFs) attract growing interest as drug nanocarriers. However, engineering “stealth” nanoMOFs with poly(ethylene glycol) (PEG) coatings remains a main challenge. Here we address the goal of coating nanoMOFs with biodegradable she...

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Published in:International journal of pharmaceutics 2021-12, Vol.610, p.121230-121230, Article 121230
Main Authors: Qiu, Jingwen, Li, Xue, Rezaei, Mahsa, Patriarche, Gilles, Casas-Solvas, Juan M., Moreira-Alvarez, Borja, Costa Fernandez, Jose Manuel, Encinar, Jorge R., Savina, Farah, Picton, Luc, Vargas-Berenguel, Antonio, Gref, Ruxandra
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cited_by cdi_FETCH-LOGICAL-c412t-72b24c3c07ae958d6e85e30f3775e2e16a11b475e6535916d7eec0de0de1b8813
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container_title International journal of pharmaceutics
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creator Qiu, Jingwen
Li, Xue
Rezaei, Mahsa
Patriarche, Gilles
Casas-Solvas, Juan M.
Moreira-Alvarez, Borja
Costa Fernandez, Jose Manuel
Encinar, Jorge R.
Savina, Farah
Picton, Luc
Vargas-Berenguel, Antonio
Gref, Ruxandra
description [Display omitted] Highly porous nanoscale metal–organic frameworks (nanoMOFs) attract growing interest as drug nanocarriers. However, engineering “stealth” nanoMOFs with poly(ethylene glycol) (PEG) coatings remains a main challenge. Here we address the goal of coating nanoMOFs with biodegradable shells using novel cyclodextrin (CD)-based oligomers with a bulky structure to avoid their penetration inside the open nanoMOF porosity. The PEG chains were grafted by click chemistry onto the CDs which were further crosslinked by citric acid. Advantageously, the oligomers’ free citrate units allowed their spontaneous anchoring onto the nanoMOFs by complexation with the iron sites in the top layers. Up to 31 wt% oligomers could be firmly attached by simple incubation with the nanoMOFs in an aqueous medium. Moreover, the anticancer drug doxorubicin (DOX) was successfully entrapped in the core–shell nanoMOFs with loadings up to 41 wt%. High resolution STEM (HR-STEM) showed that the organized crystalline structures were preserved. Remarkably, at the highest loadings, DOX was poorly released out of the nanoMOFs at pH 7.4 (
doi_str_mv 10.1016/j.ijpharm.2021.121230
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subjects Doxorubicin
Metal-Organic Frameworks
Nanoparticles
Neoplasms
Pharmaceutical Preparations
Poly(ethylene glycol) (PEG)
Porosity
Surface modification
title Porous nanoparticles with engineered shells release their drug cargo in cancer cells
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