Dual-targeted peptide-conjugated multifunctional fluorescent probe with AIEgen for efficient nucleus-specific imaging and long-term tracing of cancer cells
Precisely targeted transportation of long-term tracing regent to nucleus with low toxicity is one of the most challenging concerns in revealing the cancer cell behaviours. Here, we report a dual-targeted peptide-conjugated multifunctional fluorescent probe (RGD-NLS-CPP-cNGR-PyTPE, TNCTP) with aggregation-induced emission (AIE) characteristic, for efficient nucleus-specific imaging, long-term and low-toxicity tracing of cancer cells. TNCTP mainly consists of two components: one is the functionalized combinatorial peptides (TNCT) contains two targeted peptide (RGD and cNGR), a nuclear localization signal (NLS) and a cell penetrating peptide (CPP), which can specific bind to cell surface and effective enter into nucleus; the other one is the AIE-active tetraphenylethene derivative (PyTPE, a typical AIEgen) as fluorescence imaging reagent. In the presence of integrin αvβ3 and aminopeptidase N (CD13), TNCTP can specific bind to both of them using RGD and cNGR, respectively, lighting up its yellow fluorescence. Because of CPP, TNCTP can be effectively integrated into the cytoplasm, and then be delivered into nucleus with the help of NLS. TNCTP exhibited strong fluorescence in nucleus of the integrin αvβ3 and CD13 overexpression cells due to the specific-targeting ability, efficient transport capacity and aggregation induced emission characteristic in more crowded space. Furthermore, TNCTP can be applied for long-term tracing in living cells and scarcely affect the normal cells with negligible toxicity more than ten times passages.