Experimental evaluation of Nilotinib and Paclitaxel co-delivered via albumin nanoparticles as a therapeutic strategy for lung squamous cell carcinoma

Abstract

Chemotherapy remains the primary treatment for advanced lung squamous cell carcinoma (LUSC); however, its severe toxic side effects significantly limit therapeutic efficacy. There is an urgent clinical need to integrate molecular targeting with chemotherapy to enhance treatment outcomes. Consequently, this study developed a co-loaded albumin-based nanodelivery system (NLB/PTX-NPs) for targeted delivery of nilotinib alongside the chemotherapeutic agent paclitaxel. We systematically evaluated its in vitro and in vivo anti-tumor activity, safety, and underlying molecular mechanisms. NLB/PTX-NPs were synthesized via the solvent displacement method, followed by characterization of their physicochemical properties, drug-loading performance, and biosafety. Using NCI-H520 cells as a model, the in vitro efficacy and molecular mechanisms were evaluated through cellular uptake studies, cytotoxicity assessments, in vitro cellular experiments, and Western Blot assays. Additionally, subcutaneous tumor and lung metastasis models were established in nude mice to evaluate in vivo targeted distribution, as well as anti-tumor and anti-metastatic activities. NLB/PTX-NPs exhibited a uniform spherical morphology, demonstrating excellent dispersibility, stability, and biosafety. In vitro experiments revealed that the nanoparticles significantly enhanced cellular uptake and inhibited the proliferation, migration, and invasion of NCI-H520 cells. Western blot analysis confirmed their ability to regulate the expression of proteins associated with apoptosis and epithelial-mesenchymal transition (EMT). Furthermore, in vivo experiments indicated that the nanoparticles significantly accumulated in tumor tissues, synergistically inhibiting tumor growth ( P < 0.001) and lung metastasis ( P < 0.05) through the downregulation of NF-κB and IKBα phosphorylation levels, as well as a reduction in the Ki67 index, without any apparent systemic toxicity. This study successfully developed NLB/PTX-NPs, achieving effective co-loading of dual drugs, efficient enrichment, and synergistic delivery at tumor sites. The system demonstrated promising preclinical anti-tumor and anti-metastatic effects in the NCI-H520 models by synergistically inhibiting the NF-κB pathway, thereby providing a novel strategy for the treatment of lung squamous cell carcinoma.