Biotinylated and fluorophore-incorporated polymeric mixed micelles for tumor cell-specific turn-on fluorescence imaging of Al3+

The excessive amounts of Al3+ ion in human body can cause adverse effects on immune function and induce several neurodegenerative disorders. So far, most of the reported fluorescent probes for Al3+ present some common drawbacks, such as low sensitivity and poor water solubility. Additionally, a number of traditional fluorescent probes failed to image Al3+ in tumor cell due to the lack of tumor cell targeting and cell penetrating abilities. To overcome these shortcomings, we constructed tumor-targeting fluorescent mixed nano-micelles (mPEG-Dye-Biotin) with an average particle size of 21 nm from an amphiphilic polymer containing schiff-base fluorescent unit (mPEG-Dye) and another amphiphilic polymer containing tumor cell recognition ligand (DSPE-PEG-Biotin), through the co-self-assembly of both amphiphilic polymers in water via the film rehydration method. The as-prepared nanoprobe showed a highly sensitive and selective turn-on fluorescence response to Al3+ in aqueous solution with detection limit of 2.02×10-8 M. MTT assay revealed the negligible cytotoxicity of mPEG-Dye-Biotin nanoprobe to both HeLa cells and COS-7 cells, indicating the safety of mPEG-Dye-Biotin for biological applications. More importantly, the biotinylated nanoprobe showed better ability to enter biotin receptor-positive HeLa cells than that of non-biotinylated micelles mPEG-Dye, which made it more suitable for the detection of Al3+ ion in biotin receptor-positive tumor cells. This work provides a simple and general strategy to design highly sensitive and tumor cell-specific metal ion nanoprobe, which can be applied not only in Al3+ imaging, but also canbe extended to other ions or biomolecules by changing the incorporated fluorescent unit in the amphiphilic polymer.