Preparation and characterization of PEGylated liposomal Doxorubicin targeted with leptin-derived peptide and evaluation of their anti-tumor effects, in vitro and in vivo in mice bearing C26 colon carcinoma
2021
Shahraki, Naghmeh | Mehrabian, Amin | Amiri-Darban, Shahrazad | Moosavian, Seyedeh Alia | Jaafari, Mahmoud Reza
Employing targeting ligands on the surface of liposomes has the great potential to improve therapeutic efficacy and decreases off-target effects of liposomal formulations. In the present study, a leptin-derived peptide (Lp31) was evaluated to optimize the therapeutic efficacy of PEGylated liposomal Doxorubicin (PLD, Caelyx®). 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. Lp31, as targeting ligand, was conjugated to Maleimide-PEG2000-DSPE and then post-inserted into Caelyx. The anti-tumor activity and therapeutic efficacy of leptin modified Caelyx were evaluated and compared with Caelyx. The in vitro experiments demonstrated enhanced cytotoxicity and cellular uptake of Lp31-targeted Caelyx in C26 cell line compared to Caelyx. In BALB/c mice bearing C-26 murine carcinoma, Lp31 modified Caelyx groups exhibited significantly higher doxorubicin concentration at tumor tissue. Furthermore, Lp31 modified Caelyx at the dose of 10 mg/kg resulted in significant tumor growth inhibition and enhanced survival time compared to Caelyx. According to these results, the novel Lp31-liposomal doxorubicin offers great promise for the treatment of colon cancer and merits further investigation.
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