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  • Title: Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor.
    Author: Amiri Darban S, Nikoofal-Sahlabadi S, Amiri N, Kiamanesh N, Mehrabian A, Zendehbad B, Gholizadeh Z, Jaafari MR.
    Journal: Colloids Surf B Biointerfaces; 2018 Apr 01; 164():107-115. PubMed ID: 29413587.
    Abstract:
    Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. In the present study, the function of a leptin-derived peptide (LP16, 91-110 of Leptin) was investigated as a targeting ligand to decorate PEGylated liposomal doxorubicin (PLD, Doxil®) surface and the anti-tumor activity and therapeutic efficacy of Doxil in C26 (Colon Carcinoma) tumor model were also evaluated. As a result of this, Doxil with different LP16 peptide density (25, 50, 100 and 200 peptide on the surface of each liposome) was successfully prepared and characterized. In vitro results showed significant enhanced cytotoxicity and cellular binding and uptake of LP16-targeted Doxil formulations (LP16-Doxil) in C26 cells as compared to Doxil. In BALB/c mice bearing C26 murine carcinoma, at a dose of 15 mg/kg, LP16-Doxil groups (100 ligand) significantly suppressed the growth of the tumor and showed higher inclination to tumor as compared to non-targeted Doxil. This study revealed that the potential of LP16 peptide targeting increased the therapeutic efficacy of Doxil and highlighted the importance of optimizing the ligand density to maximize the targeting ability of the nanocarriers and merits further investigations.
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