Targeting the MUC1 tumor marker with an antibody improves the therapeutic efficacy of PEGylated liposomal doxorubicin in colon carcinoma.

Abstract Active targeting and ligand-mediated delivery are promising techniques to improve the therapeutic efficacy of drug delivery systems. In this study, we used an antibody against Mucin 1 (MUC1), which is one of the main tumor markers associated with Cancer Stem Cells (CSCs), to enhance the therapeutic efficacy of PEGylated liposomal doxorubicin (Doxil). Our results showed that MUC1-targeted Doxil (MUC1-Doxil) had significantly enhanced cellular uptake in C-26 cells compared to Doxil, as indicated by flow cytometry analyses and confocal laser scanning microscopy (CLSM). To evaluate the anti-tumor activity, therapeutic efficacy, pharmacokinetic, and biodistribution, we tested Doxil and MUC1-Doxil on BALB/c mice bearing C-26 colon carcinoma. Our findings indicated that MUC1-Doxil at a dose of 15 mg/kg showed significantly greater tumor growth inhibition and increased survival rate compared to Doxil. Therefore, modifying Doxil with the MUC1 antibody resulted in an improved therapeutic outcome. Our study demonstrated the applicability of developing a targeted delivery system for efficient delivery of DOX to tumor cells using anti-MUC1 antibody, which holds great promise for a variety of tumorassociated antigens and CSC markers in various cancer models.