Development of a NIR fluorescent probe for fluorescence-assisted EGFR-TKI applicable patients screening and drug resistance monitoring

EGFR tyrosine kinase inhibitor exerts significant benefits to non-small cell lung cancer patient, but was also limited by the applicable patient screening and drug resistance. Here we presented with an EGFR-targeted and reactive oxygen species-responsive NIR probe (LX) to achieve both patient screening and drug resistance monitoring for EGFR-tyrosine kinase inhibitor. LX inherited EGFR selectivity and preference from EGFR-tyrosine kinase inhibitor, which only showed specificity to tumor with EGFR mutation. Meanwhile, the near-infrared fluorescence of LX was initially inhibited and could be turned on by intratumoral reactive oxygen species. When LX could bind to tumor EGFR, reactive oxygen species-responsive specific fluorescence was generated to indicate the applicability of tumors to EGFR-tyrosine kinase inhibitor. However, no specific LX fluorescence could be observed in inapplicable tumors due to the lack of specificity between tumor EGFR and LX. Meanwhile, when drug resistance was developed during treatments, obvious intratumoral reactive species oxygen decrease happened, which was also deemed as a significant signal of the drug resistance. By visualizing intratumoral reactive oxygen species fluctuation by responsive fluorescence, drug resistance could be monitored and reported.