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Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes
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    Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes
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    Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering, Brooklyn, New York 11201, United States
    Department of Biomedical Engineering, State University of New York Downstate Medical Center, Brooklyn, New York 11203, United States
    § Department of Radiology, New York University School of Medicine, New York, New York 10016, United States
    Department of Chemistry, New York University, New York, New York 10003, United States
    Department of Biochemistry, SUNY Downstate Medical Center, Brooklyn, New York 11203, United States
    # Center for Genomics and Systems Biology, New York University, New York, New York 10003, United States
    Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, New York 10009, United States
    Center for Computational Biology, Flatiron Institute, Simons Foundation, 162 Fifth Avenue, New York, New York 10010, United States
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    Biomacromolecules

    Cite this: Biomacromolecules 2017, 18, 9, 2688–2698
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    https://doi.org/10.1021/acs.biomac.7b00203
    Published July 7, 2017
    Copyright © 2017 American Chemical Society

    Abstract

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    An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

    Copyright © 2017 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.7b00203.

    • Doxorubicin docking in CSP, SDS-PAGE analysis of protein expression and purification, confocal microscopy, flow cytometry histograms, quantification of cell viability studies, and relative cell viability data. (PDF)

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    This article is cited by 15 publications.

    1. Temiloluwa Majekodunmi, Dustin Britton, Jin Kim Montclare. Engineered Proteins and Materials Utilizing Residue-Specific Noncanonical Amino Acid Incorporation. Chemical Reviews 2024, 124 (15) , 9113-9135. https://doi.org/10.1021/acs.chemrev.3c00855
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    6. Jonathan W. Sun, Joseph S. Thomas, Julia M. Monkovic, Halle Gibson, Akash Nagapurkar, Joseph A. Frezzo, Priya Katyal, Kamia Punia, Farbod Mahmoudinobar, P. Douglas Renfrew, Jin Kim Montclare. Supercharged coiled‐coil protein with N‐terminal decahistidine tag boosts siRNA complexation and delivery efficiency of a lipoproteoplex. Journal of Peptide Science 2024, 30 (8) https://doi.org/10.1002/psc.3594
    7. Dustin Britton, Jonathan W. Sun, P. Douglas Renfrew, Jin Kim Montclare. Design of Coiled-Coil Protein Nanostructures for Therapeutics and Drug Delivery. Annual Review of Chemical and Biomolecular Engineering 2024, 15 (1) , 25-50. https://doi.org/10.1146/annurev-chembioeng-100722-122348
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    10. Stanley Chu, Andrew L Wang, Aparajita Bhattacharya, Jin Kim Montclare. Protein based biomaterials for therapeutic and diagnostic applications. Progress in Biomedical Engineering 2022, 4 (1) , 012003. https://doi.org/10.1088/2516-1091/ac2841
    11. Made Angga Akwiditya, Chean Yeah Yong, Mohd Termizi Yusof, Abdul Razak Mariatulqabtiah, Kok Lian Ho, Wen Siang Tan. Hepatitis B Virus-Like Particle: Targeted Delivery of Plasmid Expressing Short Hairpin RNA for Silencing the Bcl-2 Gene in Cervical Cancer Cells. International Journal of Molecular Sciences 2021, 22 (5) , 2320. https://doi.org/10.3390/ijms22052320
    12. Tamanna Islam, Md Mahedi Hasan, A. J. Saleh Ahammad, Md Nurunnabi. Microorganism-mediated drug delivery. 2021, 15-38. https://doi.org/10.1016/B978-0-12-821352-0.00007-1
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    14. Tahereh Fatemian, Hamid Reza Moghimi, Ezharul Hoque Chowdhury. Intracellular Delivery of siRNAs Targeting AKT and ERBB2 Genes Enhances Chemosensitization of Breast Cancer Cells in a Culture and Animal Model. Pharmaceutics 2019, 11 (9) , 458. https://doi.org/10.3390/pharmaceutics11090458
    15. Yao Wang, Priya Katyal, Jin Kim Montclare. Protein‐Engineered Functional Materials. Advanced Healthcare Materials 2019, 8 (11) https://doi.org/10.1002/adhm.201801374

    Biomacromolecules

    Cite this: Biomacromolecules 2017, 18, 9, 2688–2698
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.7b00203
    Published July 7, 2017
    Copyright © 2017 American Chemical Society

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