Heparin-Engineered Mesoporous Iron Metal-Organic Framework Nanoparticles: Toward Stealth Drug Nanocarriers

• Published in: Advanced healthcare materials Vol. 4; no. 8; pp. 1246 - 1257
• Main Authors: Bellido, Elena, Hidalgo, Tania, Lozano, Maria Victoria, Guillevic, Mazheva, Simón-Vázquez, Rosana, Santander-Ortega, Manuel J., González-Fernández, África, Serre, Christian, Alonso, Maria J., Horcajada, Patricia
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 03.06.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Cell Line, Tumor; Cell Survival; cell uptake; Chemical Phenomena; Coated Materials, Biocompatible - chemistry; Cytokines - metabolism; Delayed-Action Preparations; Drug Delivery Systems; heparin; Heparin - chemistry; Humans; Iron - chemistry; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Metal Nanoparticles - chemistry; metal-organic frameworks; Mice; Nanoparticles; Porosity; porous; Reactive Oxygen Species - metabolism; heparin; porous; nanoparticles; cell uptake; metal-organic frameworks
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201400755

The specific modification of the outer surface of the promising porous metal‐organic framework nanocarriers (nanoMOFs) preserving their characteristic porosity is still a major challenge. Here a simple, fast, and biofriendly method for the external functionalization of the benchmarked mesoporous iron(III) trimesate nanoparticles MIL‐100(Fe) with heparin, a biopolymer associated with longer‐blood circulation times is reported. First, the coated nanoparticles showed intact crystalline structure and porosity with improved colloidal stability under simulated physiological conditions, preserving in addition its encapsulation and controlled release capacities. The effect of the heparin coating on the nanoMOF interactions with the biological environment is evaluated through cell uptake, cytotoxicity, oxidative stress, cytokine production, complement activation, and protein adsorption analysis. These results confirmed that the heparin coating endowed the nanoMOFs with improved biological properties, such as reduced cell recognition, lack of complement activation, and reactive oxygen species production. Overall, the ability to coat the surface of the nanoMOFs using a simple and straight‐forward approach could be taken as a way to enhance the versatility and, thus, the potential of porous MOF nanoparticles in biomedicine. A green one‐pot grafting method allows the selective external surface modi­fication of a promising biocompatible mesoporous metal organic framework nanocarrier, while preserving their crystalline structure and porosity, and so their loading and controlled release abilities. In addition, heparin coating endows the nanoparticles with an improved colloidal stability and a reduced cell recognition and uptake.