INTRODUCTION: Lung cancer, a deadly malignancy, often employs Docetaxel (DTX) as a chemotherapy option. However, DTX non-selective distribution limits its therapeutic effectiveness due to adverse side effects. This study aims to develop novel folate-targeted albumin polyester nanocarriers (FA-DTX-APs) encapsulating DTX for precise delivery, enhancing lung cancer treatment efficacy. METHODS: FA-DTX-APs were meticulously crafted utilizing the thin-film dispersion technique and subsequently evaluated for their physicochemical characteristics, encapsulation efficiency, and drug release profiles. To assess their biological properties, anti-tumor efficacy, and biosafety in the context of lung cancer, a comprehensive series of hemolysis assays, cellular studies, and animal experiments were conducted. RESULTS: FA-DTX-APs exhibit nanovesicle properties with a size of (223.65 ± 6.83) nm, a potential of (26.76 ± 3.15) mV, and encapsulate DTX with high efficiency (96.19 ± 3.27%) and loading capacity (9.75 ± 0.38%). FA-DTX-APs enable tumor-targeted drug delivery and slow release of the drug over a long period of time, with faster release in acidic environments. By efficiently targeting and entering lung cancer cells, FA-DTX-APs effectively hinder cancer growth (P <
0.05), demonstrating superior anti-tumor effects (P <
0.05), biocompatibility and enhanced biological safety (P <
0.05). CONCLUSION: This study introduces FA-DTX-APs, an innovative nanocarrier characterized by exceptional biocompatibility and safety. It successfully targets lung cancer cells to deliver DTX in a sustained, slow-release manner, ensuring prolonged tumor-killing effects. As such, FA-DTX-APs hold immense promise as a novel nanoagent for lung cancer therapy.