Construction of a novel amphiphilic peptide paclitaxel rod micelle: Demonstrating that the nano-delivery system shape can affect the cellular uptake efficiency of paclitaxel and improve the therapeutic efficacy for breast cancer

Recent studies have shown that the morphology of nano-delivery systems has become a key factor affecting their anti-tumor effects. Although it has been demonstrated that rod-like nanoparticles are more easily absorbed by tumor cells, the application of rod-like nanoparticles is still limited by the lack of safe vector in vivo. In this study, a biocompatible amphiphilic peptide (IIQQQQ, I2Q4), was designed to form rod-like micelles. The key forces of the self-assembly mechanism were investigated. Driven by hydrogen bonds, the hydrophilic segment of the peptide formed a beta-sheet structure, and the molecules accumulated and extended along the side chain direction to form a rod-like structure. Using paclitaxel (PTX) as the model drug, a PTX rod-like nano-drug delivery system, PTX@I2Q4, was constructed. PTX exists in a randomly coiled state in the hydrophobic cavity formed by the peptide. Compared to PTX and spherical PTX albumin nanoparticles, PTX@I2Q4 showed higher entry efficiency and better antitumor effects in vivo and in vitro. This was mainly because PTX@I2Q4 not only allowed more efficient entry into cells via macro-pinocytosis, but also significantly prolonged the t1/2 of PTX. The results confirmed the feasibility of regulating the morphology of nanoparticles to improve the efficacy of PTX and provide a reference for further research on the influence of the morphology of the nano-drug delivery system on the efficacy of antitumor effects.