Folic acid-targeted albumin nanoliposomes co-loaded with paclitaxel and doxorubicin for enhanced treatment of lung cancer.

Lung cancer is a leading cause of cancer-related deaths globally. Co-delivery of chemotherapeutic agents with distinct properties via nanocarriers can enhance efficacy and reduce side effects. This study developed a novel targeted dual-drug delivery sustained-release nanomedicine to achieve precise therapy for lung cancer. Folic acid (FA)-targeted albumin nanoliposomes co-loaded with paclitaxel (PTX) and doxorubicin (DOX) (FA-ANLis-PTX-DOX) were prepared by reverse evaporation. The physicochemical properties were evaluated, and the drug loading efficiency and release profiles were tested. Hemolysis assays assessed the biological performance of the drug, while cell and animal studies evaluated the biosafety and antitumor activity of the nanomedicine. FA-ANLis-PTX-DOX had a size of 243.61 ± 5.84 nm, a zeta potential of 29.42 ± 4.77 mV, and high encapsulation efficiencies (PTX: 93.72 ± 4.13%; DOX: 94.24 ± 4.86%). The formulation showed sustained, pH-responsive drug release, with accelerated release under acidic conditions (pH 5.3). It exhibited low cytotoxicity against normal cells, high uptake in folate receptor-overexpressing lung cancer cells (A549, NCI-H1975), and minimal hemolysis (< 1%). In vivo, FA-ANLis-PTX-DOX significantly inhibited tumor growth and metastasis in A549 xenograft models, improved survival, and showed a favorable safety profile. The successfully developed FA-ANLis-PTX-DOX demonstrates favorable physicochemical properties, active targeting, pH-triggered release, and enhanced antitumor efficacy with good biocompatibility. This targeted co-delivery system presents a promising strategy for the precise treatment of lung cancer.