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  • Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis

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    Hutmacher383769-Published.pdf (4.022Mb)
    File version
    Accepted Manuscript (AM)
    Author(s)
    Landgraf, M
    Lahr, CA
    Kaur, I
    Shafiee, A
    Sanchez-Herrero, A
    Janowicz, PW
    Ravichandran, A
    Howard, CB
    Cifuentes-Rius, A
    McGovern, JA
    Voelcker, NH
    Hutmacher, DW
    Griffith University Author(s)
    Hutmacher, Dietmar W.
    Year published
    2020
    Metadata
    Show full item record
    Abstract
    In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy. Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth ...
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    In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy. Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth factor receptor (EGFR)-targeting antibody (Ab) cetuximab to generate a soluble and targeted nanoscale delivery vehicle for cancer treatment. After confirming the cytotoxic effect of targeted CPT-loaded pSiNP in vitro on MDA-MB-231BO cells, nanoparticles were studied in a humanized BCa bone metastasis mouse model. Humanized tissue-engineered bone constructs (hTEBCs) provided a humanized microenvironment for BCa bone metastases in female NOD-scid IL2Rgnull (NSG) mice. Actively targeted CPT-loaded pSiNP led to a reduction of orthotopic primary tumor growth, increased survival rate and significant decrease in hTEBC and murine lung, liver and bone metastases. This study demonstrates that targeted delivery via pSiNP is an effective approach to employ CPT and other potent anti-cancer compounds with poor pharmacokinetic profiles in cancer therapy.
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    Journal Title
    Biomaterials
    Volume
    240
    DOI
    https://doi.org/10.1016/j.biomaterials.2020.119791
    Copyright Statement
    © 2020 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Oncology and carcinogenesis
    Biomaterials
    Bone metastases
    Chemotherapy
    Drug delivery
    Humanized animal model
    Porous silicon
    Publication URI
    http://hdl.handle.net/10072/413302
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    • Journal articles

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