TY - JOUR
T1 - Design and Development of Biomimetic Nanovesicles Using a Microfluidic Approach
AU - Molinaro, Roberto
AU - Evangelopoulos, Michael
AU - Hoffman, Jessica R.
AU - Corbo, Claudia
AU - Taraballi, Francesca
AU - Martinez, Jonathan O.
AU - Hartman, Kelly A.
AU - Cosco, Donato
AU - Costa, Giosue'
AU - Romeo, Isabella
AU - Sherman, Michael
AU - Paolino, Donatella
AU - Alcaro, Stefano
AU - Tasciotti, Ennio
N1 - Funding Information:
M.E. and J.R.H. contributed equally to this work. The authors thank D. A. Engler, R. K. Matsunami, and the HMRI Proteomics Programmatic Core Laboratory for mass spectrometry analyses. The authors acknowledge the Sealy Center for Structural Biology and Molecular Biophysics at the University of Texas Medical Branch at Galveston for providing research resources. This work was supported by grants RF-2010-2318372 and RF-2010-2305526 from the Italian Ministry of Health, William Randolph Hearst Foundation, The Regenerative Medicine Program Cullen Trust for Health Care (Project ID: 18130014), Brown Foundation (Project ID:18130011), the Hearst Foundation (Project ID: 18130017), the NIH/NCI and the Office of Research on Women’s Health (Grant # 1R56CA213859), and Cancer Prevention and Research Institute of Texas (Project ID: RP170466) to E.T. The authors acknowledge the George J. and Angelina P. Kostas Charitable Foundation and CARIPARO Foundation Ricerca Pediatrica 2016–2018 Grant. HUVECs were purchased from ATCC (PCS-100-010). Human blood was obtained from the Houston Methodist Blood Bank (IRB ID: Pro00012800). Note: The article keywords were revised on April 9, 2018, after initial publication online.
Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/4/12
Y1 - 2018/4/12
N2 - The advancement of nanotechnology toward more sophisticated bioinspired approaches has highlighted the gap between the advantages of biomimetic and biohybrid platforms and the availability of manufacturing processes to scale up their production. Though the advantages of transferring biological features from cells to synthetic nanoparticles for drug delivery purposes have recently been reported, a standardizable, batch-to-batch consistent, scalable, and high-throughput assembly method is required to further develop these platforms. Microfluidics has offered a robust tool for the controlled synthesis of nanoparticles in a versatile and reproducible approach. In this study, the incorporation of membrane proteins within the bilayer of biomimetic nanovesicles (leukosomes) using a microfluidic-based platform is demonstrated. The physical, pharmaceutical, and biological properties of microfluidic-formulated leukosomes (called NA-Leuko) are characterized. NA-Leuko show extended shelf life and retention of the biological functions of donor cells (i.e., macrophage avoidance and targeting of inflamed vasculature). The NA approach represents a universal, versatile, robust, and scalable tool, which is extensively used for the assembly of lipid nanoparticles and adapted here for the manufacturing of biomimetic nanovesicles.
AB - The advancement of nanotechnology toward more sophisticated bioinspired approaches has highlighted the gap between the advantages of biomimetic and biohybrid platforms and the availability of manufacturing processes to scale up their production. Though the advantages of transferring biological features from cells to synthetic nanoparticles for drug delivery purposes have recently been reported, a standardizable, batch-to-batch consistent, scalable, and high-throughput assembly method is required to further develop these platforms. Microfluidics has offered a robust tool for the controlled synthesis of nanoparticles in a versatile and reproducible approach. In this study, the incorporation of membrane proteins within the bilayer of biomimetic nanovesicles (leukosomes) using a microfluidic-based platform is demonstrated. The physical, pharmaceutical, and biological properties of microfluidic-formulated leukosomes (called NA-Leuko) are characterized. NA-Leuko show extended shelf life and retention of the biological functions of donor cells (i.e., macrophage avoidance and targeting of inflamed vasculature). The NA approach represents a universal, versatile, robust, and scalable tool, which is extensively used for the assembly of lipid nanoparticles and adapted here for the manufacturing of biomimetic nanovesicles.
KW - bioinspired approach
KW - inflammation
KW - membrane protein incorporation
KW - microfluidics
KW - molecular dynamics
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U2 - 10.1002/adma.201702749
DO - 10.1002/adma.201702749
M3 - Article
C2 - 29512198
AN - SCOPUS:85043262072
SN - 0935-9648
VL - 30
JO - Advanced Materials
JF - Advanced Materials
IS - 15
M1 - 1702749
ER -