Mitochondria play an essential role in cancer initiation and progression. Research in the past decades suggested a close relation between mitochondrial dysfunction and cancer, including non-small cell lung cancer (NSCLC). In addition, mitochondrial dysfunction causes excess levels of reactive oxygen species (ROS) generation and induces mitophagy for removing damaged mitochondrial. Therefore, the induction of mitophagy against abnormal mitochondria in cancer cells is expected to be a therapeutic strategy for cancer. In this study, we aimed to develop a mitochondria-targeted delivery system for inducing mitophagy-mediated apoptosis in non-small cell lung cancer (NSCLC). We successfully synthesized amphiphilic glycol chitosan conjugated with a disulfide linker (aGCSS) and modified paclitaxel with triphenylphosphonium (PTX-TPP prodrug). These components were used to fabricate redox-sensitive nanoparticles loaded with PTX-TPP (aGC-SS-proPTX NPs). The aGC-SS-proPTX NPs exhibited controlled drug release triggered by high glutathione (GSH) levels and showed enhanced accumulation within the mitochondria due to the triphenylphosphonium modification. In vitro experiments demonstrated that the aGC-SH-proPTX NPs effectively suppressed ATP levels, induced mitophagy, and promoted apoptosis in N...