Nanotechnology-Enabled Precision Therapy for Lung Cancer in Never-Smokers

Area of Science:

• Oncology
• Nanotechnology
• Pharmacology

Background:

• Lung cancer in never-smokers (LCINS) is driven by specific oncogenic alterations and has low tumor mutational burden.
• Tyrosine kinase inhibitors (TKIs) show initial efficacy but face limitations like poor pharmacokinetics, limited central nervous system (CNS) penetration, and resistance.
• Biological barriers in LCINS include inefficient vasculature, dense extracellular matrix, efflux transporters, and immunosuppressive niches, often complicated by brain metastases.

Purpose of the Study:

• To review the current applications of nanotechnology in drug delivery systems for LCINS.
• To evaluate how nanocarriers can overcome biological barriers and enhance targeted therapies.
• To explore strategies for improving the efficacy and durability of response to LCINS treatments.

Main Methods:

• A structured literature search was performed using PubMed and Web of Science (January 2022 to November 2025).
• The review focused on studies detailing nanocarrier preparation, physicochemical properties, and therapeutic performance in preclinical models.
• Included data on pharmacokinetic and clinical outcomes of nanocarrier-based therapies for LCINS.

Main Results:

• Nanocarrier platforms can improve drug solubility, circulation time, and targeting to tumors and the CNS.
• Co-delivery systems combining TKIs with nucleic acid therapeutics show potential for modulating multiple pathways and overcoming resistance.
• Stimuli-responsive nanocarriers offer advanced therapeutic strategies for LCINS.

Conclusions:

• Nanotechnology presents a promising approach to enhance the efficacy and specificity of targeted therapies for LCINS.
• Overcoming biological barriers and resistance mechanisms is crucial for improving treatment outcomes.
• Clinical translation requires optimized carrier-payload combinations, scalable manufacturing, and biomarker-guided patient selection.