Drug Delivery and Translational Research - Featured Article: June 2024
Read the featured article from the June 2024 issue!
Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo
Summary:
Actively targeting nanodelivery systems have attracted considerable attention for cancer treatment, particularly for breast cancer, the most prevalent and lethal cancer in women worldwide. In this study, we successfully developed a targeted nanodelivery system using biogenic titanium dioxide nanoparticles (TNP) coated with polydopamine (PDA) and functionalized with nucleolin aptamer (AS1411 aptamer) for the controlled co-delivery of DOX and FOXM1 aptamer to enhance breast cancer treatment. The targeted nanodelivery system showed excellent stability in human and rat serums, a high loading efficiency of around 100% for both therapeutic agents, and a pH-responsive sustained drug release profile. In vitro cytotoxicity experiments revealed that our targeted nanodelivery system selectively internalized and effectively inhibited the growth of nucleolin-positive 4T1 and MCF-7 breast cancer cell lines, while had no effects on nucleolin-negative cells (CHO). The ex vivo biodistribution study demonstrated the selective internalization and longer residence time of the targeted nanodelivery systems in tumor tissues. Preclinical studies showed that a single-dose intravenous administration of the targeted nanodelivery system to female BALB/c mice with 4T1 tumors resulted in 1.7- and 1.4-fold more efficient inhibition of tumor growth compared to the free drug and the non-targeted nanodelivery system, respectively. Furthermore, body weight change and histopathological studies demonstrated the notable therapeutic efficacy with reduced adverse effects.