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HDL-Mimicking Peptide–Lipid Nanoparticles with Improved Tumor Targeting

Authors

  • Zhihong Zhang,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
    2. Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
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    • These authors contributed equally to this work.

  • Juan Chen,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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    • These authors contributed equally to this work.

  • Lili Ding,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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  • Honglin Jin,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
    2. Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
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  • Jonathan F. Lovell,

    1. Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
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  • Ian R. Corbin,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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  • Weiguo Cao,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
    2. Department of Chemistry Shanghai University Shanghai (China)
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  • Pui-Chi Lo,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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  • Mi Yang,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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  • Ming-Sound Tsao,

    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
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  • Qingming Luo,

    1. Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
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  • Gang Zheng

    Corresponding author
    1. Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
    2. Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
    • Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada).
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Abstract

Targeted delivery of intracellularly active diagnostics and therapeutics in vivo is a major challenge in cancer nanomedicine. A nanocarrier should possess long circulation time yet be small and stable enough to freely navigate through interstitial space to deliver its cargo to targeted cells. Herein, it is shown that by adding targeting ligands to nanoparticles that mimic high-density lipoprotein (HDL), tumor-targeted sub-30-nm peptide–lipid nanocarriers are created with controllable size, cargo loading, and shielding properties. The size of the nanocarrier is tunable between 10 and 30 nm, which correlates with a payload of 15–100 molecules of fluorescent dye. Ligand-directed nanocarriers targeting epidermal growth factor receptor (EGFR) are confirmed both in vitro and in vivo. The nanocarriers show favorable circulation time, tumor accumulation, and biodistribution with or without the targeting ligand. The EGFR targeting ligand is proved to be essential for the EGFR-mediated tumor cell uptake of the nanocarriers, a prerequisite of intracellular delivery. The results demonstrate that targeted HDL-mimetic nanocarriers are useful delivery vehicles that could open new avenues for the development of clinically viable targeted nanomedicine.

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