Smart Nanocarriers for Lung Cancer: Progress in Targeted Therapy,Controlled Release, and Theranostics

Introduction/Objective: Lung cancer remains one of the leading causes of cancerrelated mortality worldwide, primarily due to poor tumor targeting, systemic toxicity, and drug resistance associated with conventional therapies. This review explores recent advances in nanoparticle-based drug delivery systems designed to address these challenges and improve therapeutic outcomes. Methods: A structured literature search was performed across PubMed, Scopus, ScienceDirect, and Web of Science for studies published between 2010 and 2024. Only peer-reviewed English-language articles were included, focusing on nanoparticle synthesis, characterization, targeting strategies, therapeutic applications, and clinical evaluations in lung cancer. Studies irrelevant to lung cancer or without experimental/clinical data were excluded. Data were thematically analyzed to identify innovations, therapeutic outcomes, and translational challenges. Results: Evidence indicates that diverse nanocarriers, including solid lipid nanoparticles, liposomes, polymeric nanoparticles, and metal-based systems, improve solubility, tumor penetration, and controlled drug release while reducing systemic toxicity. Preparation methods such as solvent evaporation, ionotropic gelation, and nanoprecipitation were frequently reported. Both passive targeting via the EPR effect and active targeting using ligands or antibodies enhanced site-specific drug accumulation. Integration of nanocarriers with immunotherapy, gene therapy, and photodynamic therapy demonstrated synergistic efficacy. Early-phase clinical trials of formulations such as liposomal cisplatin and docetaxel polymeric micelles suggest improved tolerability and tumor localization. Discussion: The integration of nanocarriers with therapies like immunotherapy, gene therapy, and photodynamic therapy has demonstrated enhanced antitumor efficacy and reduced side effects. Further, the development of multifunctional nanoparticles and theranostic systems has shown promise in personalizing treatment. Artificial intelligence is emerging as a powerful tool to optimize nanoparticle design and functionality. Conclusion: Nanoparticle-based delivery systems represent a transformative approach in lung cancer therapy by overcoming major limitations of conventional treatments. Future research should emphasize stimuli-responsive and AI-optimized nanocarriers to further enhance precision, personalization, and patient outcomes.