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Abstract Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL). Whole exome profiling was conducted on 61 tumor tissue samples to identify tumor‐specific variants, which were then used to design personalized assay MarRyDa® for ctDNA detection. DNA extracted from BAL fluid and plasma were genotyped using MarRyDa® platform. Our analysis showed that histological subtypes and disease stages had significant differences in ctDNA detection rate. Furthermore, we found that DNA purified from BAL supernatants contains the highest levels of ctDNA compared with BAL precipitates and plasma; therefore, utilizing BAL supernatants for tumor detection might provide additional benefits. Finally, we demonstrated that tumor cellularity played significant roles in the design of personalized ctDNA panel which eventually impacts ctDNA detection sensitivity. We suggest setting a flexible criteria for sample quality control and utilization of BAL might benefit more patients in clinics.

Based on the safety of prussian blue (PB) in biomedical application, we prepared manganese-based prussian blue (MnPB) nanocatalysts to achieve enhanced photothermal therapy and chemodynamic therapy. And we conducted a series of experiments to explore the therapeutic effects of MnPB nanoparticles (NPs) on non-small cell lung cancer (NSCLC) in vivo and in vitro. For in vitro experiments, the MnPB NPs suppressed growth of A549 cells by reactive oxygen species upregulation and near-infrared irradiation. Moreover, the MnPB NPs could inhibit lung cancer metastasis through downregulating the matrix metalloproteinase (MMP)-2 and MMP-9 expression in A549 cells. And for in vivo experiments, the MnPB NPs inhibited the growth of xenografted tumor effectively and were biologically safe. Meanwhile, Mn2+ as a T1-weighted agent could realize magnetic resonance imaging-guided diagnosis and treatment. To sum up, the results in this study clearly demonstrated that the MnPB NPs had remarkable effects for inhibiting the growth and metastasis of NSCLC and might serve as a promising multifunctional nanoplatform for NSCLC treatment.