4.5 Article

Liposomal doxorubicin targeting mitochondria: A novel formulation to enhance anti-tumor effects of Doxil® in vitro and in vivo

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ELSEVIER
DOI: 10.1016/j.jddst.2021.102351

关键词

Breast cancer; Doxil?; Liposome; Mitochondria targeting; SS-02 peptide

资金

  1. Nanotechnology Research Center of Mashhad University of Medical Sciences [97000620]

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Targeting drug delivery vehicles to the mitochondria is a major area of interest for cancer treatment. This study demonstrated that modifying Doxil? with mitochondriotropic SS-02 peptide improved the therapeutic efficacy of liposomal formulation both in vitro and in vivo by targeting the mitochondria of tumor cells.
For the treatment of many types of cancers, targeting drug delivery vehicles to the mitochondria is a major area of interest which provides a significant strategy. This study aimed to investigate whether modifying Doxil? with mitochondriotropic SS-02 peptide could improve the therapeutic efficacy of liposomal formulation in vitro and in vivo. To this purpose, the peptide conjugation was done through the covalent coupling of the cysteine thiol group of SS-02 peptide to the pyrrole group of maleimide. The novel formulations of SS-02-Doxil? (100 and 200 peptides on Doxil? surface) were prepared by post-insertion which were well characterized. In vitro study indicated that Doxil? modification with SS-02 peptides could effectively enhance the cytotoxicity, cellular binding, and uptake in TUBO tumor cells. Moreover, the increase in caspase-3, and caspase-9 activities was observed in TUBO cells following the treatment with SS-02-Doxil? formulations that confirm the mitochondria targeting. Following the administration of formulations at 10 mg/kg doxorubicin in mice model of breast cancer, SS-02-Doxil? formulations significantly reduced the growth of tumor which improved animals? survival compared to Doxil?. Furthermore, the findings of in vitro and in vivo studies indicate that Doxil? modification with SS-02 peptide could improve the therapeutic efficacy due to targeting the mitochondria of tumor cells.

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