On-target site enriching fluorescent bioprobe for imaging of receptor tyrosine kinase in tumor

Abstract

Receptor tyrosine kinases (RTKs) are biological enzymes expressed on cell membranes that can influence cellular signaling, and their overexpression in tumor cells makes them a key route to assess relevant tumor processes. The development of a delivery system that targets and accumulates in RTKs overexpressing-cells at the on-target site is significant for the monitoring of tumor progression and clinical applications through longer tumor site signaling response under low injection frequency. Here, a host-guest nanoscale fluorescent probe SNI@ZIF-8 based on zeolitic imidazolate framework-8 (ZIF-8) and a fluorescent probe SNI constructed from receptor tyrosine kinase inhibitor was proposed and prepared for targeting RTKs and enabling prolonged fluorescence imaging in vivo. The folded conformation of the probe SNI resulted in low background fluorescence, and the unfolding of the SNI conformation upon insertion of the RTKs active pocket showed significant fluorescence enhancement thus enabling real-time detection of RTKs. The host-guest system SNI@ZIF-8 could release guest molecules due to the presence of the enzyme, emphasizing the reporting of stable fluorescent signals over time under low injection frequency. SNI@ZIF-8 could provide a signal response on the cell membrane of RTKs overexpressing cells without interference from other substances, and provided a longer fluorescent signal than SNI at equivalent number of injections in tumor-bearing mice. The host-guest system SNI@ZIF-8, with its obvious tumor site enrichment ability and clear fluorescence imaging ability, could be successfully applied to the detection of RTKs on cell membranes in biological systems, providing a new strategy for determining the process of tumor development in clinical applications.