Construction of IMMS Containing Multi-site Liposomes for Dynamic Monitoring of Blood CTC in Patients with Osimertinib-resistant Non-small-cell Lung Cancer and its Mechanism.

Objective: This article aims to establish a liquid biopsy system for gene detection of circulating tumor cells (CTC) in lung cancer, systematically analyze the significance of osimertinib resistance, and formulate an individualized diagnosis and treatment plan.

Methods: Liposome-contained magnetic microspheres coated with Fe3O4 nanoparticles were synthesized by microemulsion, and the surface was modified with EGFR antibody to form EGFR/EpCAM multi-site liposome-contained immunomagnetic microspheres (IMMSs). The CTCs were isolated and identified from peripheral blood samples and the cell lines of lung cancer patients collected by the multi-site liposome-contained IMMSs. To investigate the effects of the order of use of IMMSs sequence at different sites on the sorting and trapping efficiency of non-small-cell lung cancer (NSCLC) cells . The preliminary verification of drug-resistant gene function and dynamic monitoring of CTCs in 20 patients with EGFR-positive NSCLC were screened and statistically analyzed before and after osimertinib treatment. Sensitivity analysis and drug resistance evaluation of oxitidine were detected in vitro.

Results: Results showed the prepared multi-site liposome-contained IMMSs had high stability and specificity. The number of CTCs in blood samples of the patients with NSCLC was detected, revealing high sorting efficiency, and positive sorting rate reaching more than 90%. We investigated the effect of osimertinib on the HER-2 expression on the EGFR-mutated NSCLC cells and found that osimertinib increased the expression of HER-2 on the cell surface of NSCLC cell lines., And further explored the therapeutic potential of osimertinib combined with T-DM1 at different dosing times.

Conclusion: Our results demonstrate that the prepared multi-site liposome-contained IMMSs can efficiently isolate CTCs from the peripheral blood in lung cancer. Combined with the experimental data about osimertinib can be effectively identified, the resistant genes of NSCLC including EGFR, which will provide a new scientific basis for guiding clinical medication and formulating individualized treatment plans.