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.

The efficient delivery of Ptx by nanofibers into cancer cells to induce apoptosis by regulating the expression of p-Akt and related apoptotic proteins.100