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Metal Organic Framework (MOF) Particles as Potential Bacteria-Mimicking Delivery Systems for Infectious Diseases: Characterization and Cellular Internalization in Alveolar Macrophages

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Abstract

Purpose

Intramacrophagic bacteria pose a great challenge for the treatment of infectious diseases despite many macrophage targeted drug delivery approaches explored. The use of biomimetic approaches for treating infectious diseases is promising, but not studied extensively. The study purpose is to evaluate iron-based metal-organic frameworks (MOF) as a potential bacteria-mimicking delivery system for infectious diseases.

Methods

Two types of carboxylated MOFs, MIL-88A(Fe) and MIL-100(Fe) were developed as “pathogen-like” particles by surface coating with mannose. MOF morphology, cellular uptake kinetics, and endocytic mechanisms in 3D4/21 alveolar macrophages were characterized.

Results

MIL-88A(Fe) is rod-shape (aspect ratio 1:5) with a long-axis size of 3628 ± 573 nm and MIL-100(Fe) is spherical with diameter of 103.9 ± 7.2 nm. Cellular uptake kinetics of MOFs showed that MIL-100(Fe) nanoparticles were internalized at a faster rate and higher extent compared to MIL-88A(Fe) microparticles. Mannosylation did not improve the uptake of MIL-100(Fe) particles, whereas it highly increased MIL-88A(Fe) cellular uptake and number of cells involved in internalization. Cell uptake inhibition studies indicated that macropinocytosis/phagocytosis was the main endocytic pathway for internalization of MOFs. Accumulation of MOF particles in acidic compartments was clearly observed.

Conclusions

The successfully synthesized “pathogen-like” particles provide a novel application of MOF-based particles as biomimetic delivery system for intramacrophagic-based infections.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, South Dakota State University, 1055 Campanile Avenue, Avera Health Science Building, Brookings, SD, 57007, USA

    Ailin Guo, Mikhail Durymanov, Anastasia Permyakova & Joshua Reineke

  2. Institut des Matériaux Poreux de Paris, FRE 2000 CNRS Ecole Normale Supérieure Ecole Supérieure de Physique et de Chimie Industrielles de Paris, PSL Research University, 75005, Paris, France

    Saad Sene & Christian Serre

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  1. Ailin Guo
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  2. Mikhail Durymanov
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Correspondence to Joshua Reineke.

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Ailin Guo, Mikhail Durymanov and Anastasia Permyakova contributed equally to this work.

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Guo, A., Durymanov, M., Permyakova, A. et al. Metal Organic Framework (MOF) Particles as Potential Bacteria-Mimicking Delivery Systems for Infectious Diseases: Characterization and Cellular Internalization in Alveolar Macrophages. Pharm Res 36, 53 (2019). https://doi.org/10.1007/s11095-019-2589-4

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