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نویسندگان: Saeed Mohammadian Haftcheshmeh , Mahmoud Reza Jaafari , Seyedeh Hoda Alavizadeh , Mohammad Hasan Darvishi, Fatemeh Gheybi

زمان بندی: بدون زمان بندی

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برچسب: Nanomedicine

کد: GP-04138

خلاصه مقاله: In recent years, targeted drug delivery systems to mitochondria of cancer cells is a major area of interest in the....

In recent years, targeted drug delivery systems to mitochondria of cancer cells is a major area of interest in the field of cancer chemotherapy and provides a novel strategy in treating many cancers. Mitochondria as a key organelle in the cell, in addition to supplying cellular energy, play crucial regulatory roles in cell death or apoptosis. Doxil® is the first stable PEGylated nanoliposomal formulation of doxorubicin (Dox) that has been approved for the treatment of various types of cancers (especially blood malignancies). Doxil® is capable of prolonging the circulation half-time of Dox and lowering its clearance rate. In recent years, various types of small peptides have been characterized to targets mitochondria. The current study was set out to investigate whether modification of Doxil® with mitochondriotropic peptide SS-02 improved its anti-tumor effects and therapeutic efficacy in vitro and in vivo. To this purpose, conjugation of SS-02 peptide was done through covalent coupling of cysteine thiol group of peptide to the pyrrole group of maleimide. For the first time, a novel formulation of SS-02-Doxil® (100 and 200 peptides on the surface of Doxil®) was successfully synthesized using post-insertion method and well characterized by high Performance liquid chromatography (HPLC) and liquid chromatograph mass spectrometer (LC/MS). In vitro study showed that modification of Doxil® with SS-02 peptide effectively enhanced its cytotoxicity, cellular binding, and uptake in TUBO tumor cells. Besides, more increase in caspase-3 and caspase-9 activities was observed in TUBO cell treated with novel SS-02-Doxil® formulations. In mice model of breast cancer, following administration of formulations at a dose of 10 mg/kg doxorubicin, SS-02-Doxil® formulations significantly reduced the growth of tumor and improved the survival rate of mice bearing TUBO tumor as compared to Doxil®. Taken together, findings of in vitro and in vivo studies clearly indicate that modification of Doxil®, as a drug delivery system; with SS-02 peptide improved its anti-tumor effects and therapeutic efficacy, as a result of targeting mitochondria of cancer cells.


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