Paclitaxel (Ptx), a type of microtubule depolymerization inhibitor, is one of the main components in
gastric cancer chemotherapy. Some studies have demonstrated that
tetrandrine (Tet), a
bisbenzylisoquinoline alkaloid, has potential antitumor effects in several
cancers. Aside from the direct anticancer effect, Tet is proved to synergistically enhance the antitumor effect of Ptx in
gastric cancer. However, the application of the combinational strategy is limited by the poor solubility of both drugs. Nanodrug delivery systems including polymeric nanoparticles, self-assembled nanofibers,
hydrogels, etc., hold the potential to meet the need. Here, a novel supramolecular nanomaterial, based on the concept of "carrier-free nanodrugs", is reported as a feasible platform for synergistic
drug delivery. Ptx-SA-RGD is obtained through the conjugation of Ptx and the
tumor-specific
peptide RGD (
arginine-glycine-aspartic acid) with
succinic acid (SA) as a linker. Ptx-SA-RGD could self-assemble into Ptx nanofibers (P-NFs) with high
drug-loading efficiency. Tet was then encapsulated into P-NFs to acquire novel Ptx and Tet coloaded self-assembled nanofibers (P/T-NFs). The uptake study shows the dynamic internalization of P/T-NFs by the
gastric cancer cell line MGC-803. P/T-NFs significantly triggered the accumulation of
reactive oxygen species (ROS) in
gastric cancer cells MGC803 and further decreased the mitochondrial membrane potential, which led to the induction of mitochondrial apoptosis with superior cytotoxicity against free drugs. Moreover, P/T-NFs suppressed the expressions of p-STAT3 and p-JAK, initiated
cytochrome-C release, and promoted
caspase protein expression. Furthermore, P/T-NFs demonstrated the strongest
tumor-delaying effect as well as the lowest toxicity. Therefore, self-assembled nanofibers of P/T-NFs demonstrated an increase of the mitochondrial apoptosis level and a stronger antitumor effect both in vitro and in vivo, which could be a potential way to enhance the clinical efficacy and reduce the side-effects of Ptx in
gastric cancer.