Enhanced In Vitro and In Vivo Anticancer Properties by Using a Nanocarrier for Co-Delivery of Antitumor Polypeptide and Curcumin

: In this paper, a novel pH and redox dual-sensitive nanocarrier loaded with curcumin (Cur) and anticancer polypeptide (AP) was developed for dual targeting mitochondrial and CD44 receptor. The amphiphilic block copolymer was prepared by triphenylphosphonium (TPP)/oligomeric hyaluronic acid (oHA)/disulfide-menthone 1,2-glycerol ketal (SM), hereinafter referred to as TPP-oHSM. The TPP targeted the mitochondria, pH/redox dual-sensitive SM served as a hydrophobic part, and the CD44 receptor targeting oHA worked as a hydrophilic part. The chemical structure of the TPP-oHSM was identified using 1H NMR and FTIR technologies. Cur and AP were loaded into the TPP-oHSM micelles by self-assembly and denoted as C/A@TM. The C/A@TM prepared in this study exhibited an approximately spherical structure, with a mean diameter of 191.3 ± 3.1 nm and a negative zeta potential of -26.10 ± 0.45 mV. The in vitro release study and cellular uptake test revealed that the C/A@TM targeted the mitochondria and CD44 receptor, as well as it showed sensitivity towards pH and redox. In addition, the C/A@TM demonstrated satisfactory cytotoxic effects against MDA-MB-231 cells and MCF-7 cells. Finally, the in vivo application of the C/A@TM showed excellent therapeutic effects. The C/A@TM developed in this study exhibited promising multifunctional properties as a co-delivery carrier of polypeptide and chemical drug for an effective clinical therapy for cancer.