Superior antitumor effect of extremely high drug loading self-assembled paclitaxel nanofibers

Recent studies focused on the nanodelivery system of paclitaxel (Ptx) to overcome the poor solubility and hypersensitivity of Ptx caused by the application of Cremophor EL as a solvent. Although many studies use different types of polymers as carriers to prepare Ptx-loaded polymeric nanoparticles, the relatively low loading efficiency of Ptx-loaded polymeric nanoparticles significantly limits its application. Here, we design and synthesize a simple conjugation of Ptx and succinic acid (Ptx-SA), which can self-assemble into nanofibers and become "carrier-free" with Ptx as the drug carrier. The highest loading efficiency of Ptx is 89.5% with a controlled release pattern. The cellular uptake study indicates the internalization of Ptx-SA nanofibers by A549 cells. The in vitro cytotoxicity test results indicate that Ptx-SA nanofibers were much more effective in inhibiting the proliferation of A549 cells than free Ptx, particularly at the lower working concentration. The clonogenic assay shows the enhanced effect of Ptx-SA in ameliorating the clonogenic abilities of A549 cells compared with the equivalent dose of free Ptx. Moreover, Ptx-SA significantly attenuates the expression of p-Akt and increases the expression of cleaved PARP and Caspase-3 compared to the equivalent dose of free Ptx, which demonstrates the enhanced apoptosis-inducing effect of Ptx-SA. The animal study demonstrates the superior antitumor effect of Ptx-SA compared to free Ptx. Therefore, the conjugation of Ptx with SA enables the self-assembly of Ptx-loaded nanofibers with stronger in vitro and in vivo antitumor effects, which is a promising method to improve the therapeutic efficacy of Ptx in treating lung cancer.