Samanta da Silva Gündel, Aline de Cristo Soares Alves, Danieli Rosane Dallemole, Sı́lvia Stanisçuaski Guterres, Adriana Raffin Pohlmann
Lung cancer remains the most prevalent and lethal type of cancer worldwide, mainly due to late-stage diagnosis and resistance to standard therapies. Although systemic chemotherapy is still the primary option for advanced and metastatic cases, its effectiveness is limited by poor solubility, nonspecific tissue distribution, and severe side effects. Nanotechnology has emerged as a promising strategy to overcome these challenges, with organic nanoparticles representing a particularly innovative approach. In this context, surface-functionalized nanoparticles have shown great potential to enhance drug delivery specifically to tumor cells, reducing off-target toxicity and improving therapeutic outcomes. This review presents an overview of key strategies for surface modification of nanoparticles designed for targeted lung cancer therapy. We reported the two main functionalization approaches, through covalent and non-covalent bonds, as well as the most relevant cellular targets and the main ligands employed. Finally, the review underscores how surface modification strategies may contribute to improving the selectivity and performance of nanoparticle-based systems, offering a basis for future studies focused on their potential clinical applicability in lung cancer therapy.