Ailin Guo1, Mikhail Durymanov1, Anastasia Permyakova1, Saad Sene2, Christian Serre2, Joshua Reineke3. 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. 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. 3. 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. joshua.reineke@sdstate.edu.
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.
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.
Authors: Bader M Jarai; Zachary Stillman; Lucas Attia; Gerald E Decker; Eric D Bloch; Catherine A Fromen Journal: ACS Appl Mater Interfaces Date: 2020-08-20 Impact factor: 9.229
Authors: Maya Holay; Zhongyuan Guo; Jessica Pihl; Jiyoung Heo; Joon Ho Park; Ronnie H Fang; Liangfang Zhang Journal: ACS Appl Bio Mater Date: 2020-10-08