Targeted multifunctional redox-sensitive micelle co-delivery of DNA and doxorubicin for the treatment of breast cancer

Drug/gene co-delivery carriers are a promising strategy for cancer treatment. Thus, herein, T7-conjugated redox-sensitive amphiphilic polyethylene glycol-polyethyleneimine-poly(caprolactone)-SS-poly(caprolactone)-polyethyleneimine-polyethylene glycol (PEG-PEI-PCL-SS-PCL-PEG) (PPPT) is designed to realize the co-delivery of pORF-hTRAIL and DOX efficiently into tumor cells. PPPT is synthesized via the ring opening polymerization (ROP) of ε-caprolactone followed by Michael addition polymerization and atom transfer radical polymerization (ATRP) of the maleic imide group of MAL-PEG-NHS. The PPPT micelles present a spherical or ellipsoidal geometry with a mean diameter of approximately 100-120 nm. Meanwhile, they also exhibit a redox-responsive drug release profile in vitro. The blood compatibility and complement activation tests reveal that the PPPT micelles do not induce blood hemolysis, blood clotting, or complement activation. The T7-modified co-delivery system shows a higher cellular uptake efficiency than the unmodified co-delivery system in human breast cancer MCF-7 cells and is accumulated in tumor more efficiently in vivo. These results suggest that the T7-targeted codelivery system of DOX and pORF-hTRAIL is a combined delivery platform that can significantly improve the treatment of breast cancer.