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

α-Fe 2 O 3 /Fe 3 O 4 MHNTs were prepared by the hydrothermal and calcination-reduction method. • A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs was fabricated for its antitumor activity against A549 cells. • The delivery nanosystem exhibited excellent biocompatibility, pH responsiveness, sustained-release properties, and antitumor effects. • In vitro studies demonstrated that the cytotoxic effect on A549 cells was mainly mediated via the apoptosis pathways, accompanied by the involvement of ferroptosis. 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-Fe 2 O 3 /Fe 3 O 4 magnetic heterogeneous nanotube (MHNTs) via a hydrothermal and calcination-reduction method. After being modified with PEG 2000 and loaded with PTX, α-Fe 2 O 3 /Fe 3 O 4 -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-Fe 2 O 3 /Fe 3 O 4 -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. A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs fabricated via the hydrothermal and calcination-reduction process was constructed for antitumor. This targeted paclitaxel nanosystem exerted its cytotoxic effect on A549 human lung cancer cells by inducing apoptosis, with ferroptosis also involved in the process, confirming its potential for clinical translation in lung cancer treatment. Download: Download high-res image (129KB) Download: Download full-size image