Targeting the lung tumor microenvironment by phytochemicals and their nanoformulations

Lung malignancies are among the most prevalent and foremost causes of tumor-related deaths. Despite significant advancements in the understanding and management of lung cancer, resistance to traditional treatments remains a significant challenge. Understanding and targeting tumor microenvironment (TME) have attracted interest in the recent decade for eliminating various solid tumors. The lung TME has a crucial position in tumor expansion and therapy failure, driving it an engaging target for novel medicinal interventions. Plant-derived products offer a promising avenue for targeting TME due to their diverse chemical structures and biological activities. However, their clinical use is hindered by insufficient bioavailability and also possible systemic toxicity. The use of nanoparticles as delivery vehicles for natural products can overcome these challenges and enhance their therapeutic efficacy. This review article explores the potential of plant-derived products as medicinal agents for targeting lung TME. We provide an outline of the present knowledge of lung TME and explain the mechanisms by which plant-derived products can modulate key components of this microenvironment. The promising impacts and properties of nanoparticles for the delivery of these derivatives into lung tumors will also be discussed. We also review the preclinical and clinical findings for supporting the usefulness of these agents in targeting lung TME. Additionally, we highlight the challenges and forthcoming trends in the development of plant-derived products as targeted therapies for lung cancer, with a particular focus on combination therapies.