A Novel Aerogel Delivery System Reduces Drug Resistance for Non-Small Cell Lung Cancer Combination Therapy.

Lung cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) representing the predominant subtype. Despite advances with molecularly targeted therapies, the prognosis remains poor because of drug resistance. Combination therapy with docetaxel and gefitinib offers synergistic potential but is limited by systemic side effects from nonspecific uptake. Here, we developed an inhalable aerogel-based nanocarrier for the efficient codelivery of docetaxel and gefitinib, designed to enhance lung tumor accumulation while reducing systemic toxicity. Inhalation administration resulted in significant drug enrichment in tumors and achieved a tumor inhibition rate of 55.4% ± 3.6% in an NSCLC xenograft model, with reduced resistance compared with monotherapy. Mechanistically, the aerogel synergistically suppressed angiogenesis and promoted apoptosis. These findings underscore the potential of inhalable aerogels as a promising strategy for effective NSCLC therapy and clinical translation.