The Superior Anticancer Effect of Self-Assembled Paclitaxel Nanofibers is Mediated Through Co-Operation Between Enhanced Apoptosis and Autophagic Cell Death.

Paclitaxel (Ptx) has been recommended as one of the main components of first-line chemotherapy for gastric cancer. However, the side effects of Ptx have greatly limited its clinical application because of its poor solubility and emerging resistance. In the current study, we designed novel self-assembled Ptx nanofibers with extremely high drug loading efficiency through conjugation of Ptx with succinic acid (sa), resulting in self-assembled nanofibers without the need for additional polymeric carriers. Cytotoxicity tests showed the superior effect of Ptx-sa against the gastric cancer cell lines SCG7901 and BGC823, but there was an obvious discrepancy between the number of apoptotic cells and dead cells, which indicates that other mechanisms may be involved in Ptx-sa-induced cell death. Mechanism studies, including apoptosis and autophagy detection, showed that Ptx-sa induced apoptosis and autophagy-induced cell death more efficiently than an equivalent dose of free Ptx. Most importantly, based on TEM and transfection with dual fluorescencelabeled LC3, more autophagosomes and increased autophagic flux were elicited by Ptx-sa in gastric cancer cells than an equivalent dose of free Ptx. Western blotting demonstrated that Ptx-sa induced the expression of LC3 II, a marker of autophagy, much more effectively than free Ptx. Moreover, an in vivo study demonstrated that Ptx-sa nanofibers significantly enhanced the anti-cancer effect of Ptx. Therefore, the self-assembled Ptx-sa nanofibers may exert cytotoxicity by inducing both apoptosis and autophagic cell death and thus might be a promising strategy to strengthen the therapeutic efficacy of Ptx in gastric cancer.