Use of the MOF NU-1000 as a Drug Delivery System for the Antineoplastic Drug Mitoxantrone

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Abstract
Metal–organic frameworks (MOFs) offer unique opportunities for drug delivery due to their high porosity and the possibility of hosting large drug molecules within well-defined pore systems. In this work, the zirconium-based MOF NU-1000 was investigated as a carrier for the antineoplastic drug mitoxantrone (MTX). NU-1000 particles were synthesized and characterized by PXRD, SEM, and DLS, confirming their crystallinity, morphology, and size distribution. MTX loading was achieved by aqueous incubation and quantified by UV-Vis spectroscopy and thermogravimetric analysis, yielding a high loading capacity of ~40–43 wt%, with most of the uptake occurring within the first three hours. Structural characterization demonstrated that the MOF preserves its crystallinity and morphology after drug incorporation, while the DLS results suggest that MTX is mainly accommodated within the internal pore system. To improve stability under physiological conditions, the composite was coated with NH2-PEG-NH2, resulting in PEG@MTX@NU-1000 particles with enhanced stability in phosphate-buffered saline. Cytotoxicity assays in HeLa cells showed that the PEGylated carrier is largely biocompatible, while PEG@MTX@NU-1000 exhibits a significantly enhanced antiproliferative effect compared to free MTX at short incubation times. These results demonstrate that NU-1000 is a promising platform for MTX delivery, combining high loading capacity, structural stability after PEGylation, and improved short-term therapeutic performance.
Funding Information
  • Agencia Estatal de Investigación (10.13039/501100011033)
  • Agencia Estatal de Investigación (PCI2020-112241)
  • the European Regional Development Fund
  • Junta de Andalucía (P20_01258)

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