Abstract

The emergence of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) poses formidable obstacles to non-small cell lung cancer (NSCLC) therapy. Real-time monitoring of the efficacy of EGFR-TKIs to avoid invalid treatment remains a great challenge. Herein, we rationally designed a EGFR-TKI-modified liposomal complex co-loaded with a iodine-containing contrast agent ioversol (IOV) and a photosensitizer indocyanine green (ICG), namely ELIG, for simultaneous EGFR-TKI-mediated computed tomography/fluorescence dual-modal imaging to monitor drug resistance during the treatment, and combined photodynamic therapy (PDT) and photothermal therapy (PTT) to reverse drug resistance. ELIG exhibited good physicochemical properties, favorable photothermal effects, and high singlet oxygen production. ELIG can protect ICG and IOV from rapid degradation and prolong the circulation time. In addition, ELIG had a great ability to recognize drug-sensitive EGFR-mutated NSCLC cells, and could monitor the changes in the intracellular amounts of the imaging agents to detect the drug resistance and predict the efficacy during the treatments. Additionally, the heavy atom effect of IOV can increase the PDT effect of ICG obviously. With 808 nm laser irradiation, ELIG showed satisfactory anticancer effects to reverse drug resistance by the synergism of PDT and PTT in vitro and in vivo. Hence, this work holds great promise for providing a new idea and an effective strategy for predicting and managing the efficacy of EGFR-TKIs.

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