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

PurposeIntramacrophagic 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.MethodsTwo 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.ResultsMIL-88A(Fe) is rod-shape (aspect ratio 1:5) with a long-axis size of 3628573nm and MIL-100(Fe) is spherical with diameter of 103.9 +/- 7.2nm. 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.