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

Abstract Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of -23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-sensitive sustained drug release profile following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments exhibited the selective and effective internalization of the targeted nanodelivery system into nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that this phenomenon was not observed in nucleolin-negative cells (CHO). Moreover, the preclinical studies revealed remarkable tumor growth inhibition with lower side effects for the targeted nanodelivery system in comparison with free drug and the non-targeted nanodelivery system. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.