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Antibody-Conjugated Vitamin E-Derived Liposomes for Targeted Gene Transfer

  • Mohini Kamra
    Mohini Kamra
    Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
    Technical Research Centre, Indian Association for the Cultivation of Science, Kolkata 700032, India
    More by Mohini Kamra
  • Bappa Maiti
    Bappa Maiti
    School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India
    More by Bappa Maiti
  • Pranay Saha
    Pranay Saha
    School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India
    More by Pranay Saha
  • Anjali A. Karande
    Anjali A. Karande
    Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
  • , and 
  • Santanu Bhattacharya*
    Santanu Bhattacharya
    Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
    Technical Research Centre, Indian Association for the Cultivation of Science, Kolkata 700032, India
    School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India
    *Email: [email protected]; [email protected]; [email protected]
Cite this: ACS Appl. Bio Mater. 2020, 3, 12, 8375–8385
Publication Date (Web):November 29, 2020
https://doi.org/10.1021/acsabm.0c00656
Copyright © 2020 American Chemical Society

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    Abstract

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    Construction of a vitamin E-based liposomal biomaterial and its ability to deliver therapeutic genes selectively across liver cancer cells are demonstrated herein. In humans, liver regulates the levels of α-tocopherol, i.e., vitamin E, and hepatic cells carry the machinery for its transport. To exploit the presence of tocopherol transport protein, we have selected an efficient gene transfecting α-tocopherol-based twin lipid bearing a hydroxyethylated headgroup and octamethylene spacer (TH8S) for liposome formation. Also, based on the abundancy of the low-density lipoprotein receptor (LDLr) on the cellular surface in the case of hepatocellular carcinoma, anti-LDLr monoclonal antibody is used to confer the targeting ability to liposomes. A facile thiol–maleimide click chemistry is used for antibody decoration on the liposomal surface. Selective delivery of reporter and therapeutic genes (GFP and p53) to cells of hepatic origin was observed using anti-LDLr-tagged TH8S liposomes. Cellular internalization by receptor-mediated endocytosis renders the bioconjugate highly specific as well as highly efficient. Compatibility of the designed material with human blood points to its safety of use in systemic circulation thereby highlighting its in vivo potential. Thus, we report here a versatile biomaterial derived from an essential vitamin that promises potential for targeted suicidal gene therapy.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsabm.0c00656.

    • Synthetic scheme for tocopherol derivative and chemical characterization, PAGE for antibody purification and conjugation, ELISA and Ellman's assay calibration curves, and LDLr expression profiling data along with DLS/Zeta, AFM, TEM, DNA binding, gene transfection and apoptosis results (PDF)

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    Cited By

    This article is cited by 5 publications.

    1. Hiromasa Taniguchi, Yugo Ishimime, Kosuke Minamihata, Pugoh Santoso, Takuya Komada, Hendra Saputra, Kazuki Uchida, Masahiro Goto, Toki Taira, Noriho Kamiya. Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal Activity. Molecular Pharmaceutics 2022, 19 (11) , 3906-3914. https://doi.org/10.1021/acs.molpharmaceut.2c00388
    2. Bappa Maiti, Krishan Kumar, Subhasis Datta, Santanu Bhattacharya. Physical–Chemical Characterization of Bilayer Membranes Derived from (±) α-Tocopherol-Based Gemini Lipids and Their Interaction with Phosphatidylcholine Bilayers and Lipoplex Formation with Plasmid DNA. Langmuir 2022, 38 (1) , 36-49. https://doi.org/10.1021/acs.langmuir.1c01039
    3. Jens Casper, Laura Nicolle, Melanie Willimann, Evrim Ümit Kuzucu, Alan Tran, Perrine Robin, Pascal Detampel, Hiu Man Grisch‐Chan, Beat Thöny, Jörg Huwyler, Sandrine Gerber‐Lemaire. Core–Shell Structured Chitosan‐Polyethylenimine Nanoparticles for Gene Delivery: Improved Stability, Cellular Uptake, and Transfection Efficiency. Macromolecular Bioscience 2023, 23 (1) https://doi.org/10.1002/mabi.202200314
    4. Bappa Maiti, Santanu Bhattacharya. Liposomal n anoparticles based on steroids and isoprenoids for nonviral gene delivery. WIREs Nanomedicine and Nanobiotechnology 2022, 14 (1) https://doi.org/10.1002/wnan.1759
    5. Minjun Kim, Yelim Choi, Dae Hwan Lee, Jihyun Min, Yong‐Jin Pu, Taiho Park. Roles and Impacts of Ancillary Materials for Multi‐Component Blend Organic Photovoltaics towards High Efficiency and Stability. ChemSusChem 2021, 14 (17) , 3475-3487. https://doi.org/10.1002/cssc.202100887

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