Study on combination therapy for lung cancer through pemetrexed-loaded mesoporous polydopamine nanoparticles

Lung cancer is one of the most commonly diagnosed cancers, and surgical resection is the optimal choice for the primary lung tumor. But for the secondary lung cancer, chemotherapy and combined radiotherapy still are the main strategies. To realize the combined treatment for non-small cell lung cancer (NSCLC), in this work, a nanoplatform based on pemetrexed (PE)-loaded mesoporous polydopamine (MPDA) nanoparticles were investigated. PE, a special therapeutic drug for NSCLC, was loaded into the MPDA nanoparticles via electrostatic attraction and was encapsulated with polyvinyl pyrrolidone (PVP). The results showed that, when irradiating with 808 nm near-infrared light, the PE loaded MPDA (MPDA@PE@PVP) nanoparticles have excellent photothermal conversion properties, which would result in increase of ambient temperature and could accelerate the release of PE. In vitro cell experiments proved that MPDA@PE@PVP nanoparticles have excellent killing ability for NSCLC A549 cells by the functions of PE and photothermal ability of MPDA nanoparticles. Meanwhile, the intra-cellular reactive oxygen species (ROS) levels of A549 cells in the MPDA@PE@PVP nanoparticle-treated group could be promoted significantly after irradiation, leading to the death of A549 cells. In vivo animal model results showed that MPDA@PE@PVP nanoparticles could gather at the tumor site by enhanced permeability and retention (EPR) effect and have significant inhibition ability for lung tumor by synergistic therapy of chemotherapy, photothermal therapy and photodynamic therapy.