Construction of targeted paclitaxel delivery nanosystem and its apoptosis mechanism on A549 cells

Paclitaxel (PTX), a first-line chemotherapeutic agent, suffers from poor tumor targeting and off-site toxicity, which can easily cause damage to the hematopoietic, digestive, and nervous systems. Magnetic targeting delivery strategies offer a promising solution to address this challenge. Herein, we innovatively prepared α-Fe₂O₃/Fe₃O₄ magnetic heterogeneous nanotube (MHNTs) via a hydrothermal and calcination-reduction method. After being modified with PEG₂₀₀₀ and loaded with PTX, α-Fe₂O₃/Fe₃O₄-PEG-PTX delivery nanosystem exhibited both good biocompatibility and pH responsiveness, with an average length and average wall thickness of 174 nm and 37.9 nm, respectively. The encapsulation efficiency and drug loading efficiency of paclitaxel in the α-Fe₂O₃/Fe₃O₄-PEG-PTX nanocomposites reached 98.4% and 37.4%, individually. In vitro studies demonstrated that this nanosystem exhibited excellent magnetic responsiveness. Under the influence of a magnetic field, the viability of A549 cells decreased to 33% after 72 h of coincubation with the nanocomposite, accompanied by elevated intracellular peroxidation levels and ROS content. Further Western blot analysis of related proteins revealed that the nanocomposite induced A549 cell death via activation of the caspase-dependent apoptosis pathway, accompanied by the involvement of ferroptosis. The drug release process of this magnetic delivery nanosystem was stable and controllable, providing a promising strategy for enhancing the delivery efficiency of insoluble drugs and improving the therapeutic efficacy for lung cancer.