Synthesis And Application Of Cell-targeting CdTe Quantum Dot Probe Based On The Design Of RGD Peptide

Fluorescent semiconductor nanocrystals (quantum dots, QDs) have attracted great interest for wide application in photonic devices and bio-labeling due to their unique and fascinating optical properties. To our knowledge, quantum dots widely used in biological field are mostly synthesized in an organic phase. However, this hydrophobic TOPO layer is often neither suitable nor robust enough for biological applications. As we know, ligands used in synthesis play an important role in controlling nanoparticle properties. Recently, biomolecule offers a completely new strategy to design and synthesize complex nanostructure because of their fascinating structure and self-assembling function.In this study, we chose a series of short peptides containing RGD sequence as ligands for the synthesis of QDs. RGD is a tripeptide that consists of Arg, Gly and Asp. This peptide sequence is found in many extracellular matrix proteins like vitronectin, laminin, fibrinogen, and fibronectin. This peptide can be used to restrain adhesion and migration between tumor cell and extracellular matrix, suppress the formation of tumor blood vessel and induce opotosis of the tumor cell. First, we designed a series of RGD peptides containing RGD sequence and L-cysteine moiety (Cys) through changing the number of Cys, adjusting space between RGD and Cys, or changing function group of the peptide. Then we prepared the designed RGD peptides by Microwave Fmoc-solid phase synthesis method. The mass spectrometry and high performance liquid chromatography showed that they had high purity. Finally, they were stored in 4 oC before use.We synthesized RGD-capped CdTe QDs in aqueous soulution using as-prepared RGD peptides as stabilizer, and the synthesis conditions were optimized by changing different conditions such as pH, concentration and feed ratio. Then we chose the most appropriate tripeptide by comparing the effect of the synthetic peptide. The experiment results show that CRGDS is the most appropriate RGD peptide for the synthesis of CdTe QDs, and the best quantum yield of as-synthesized QDs can reach above 20% and the minimum FWHM can be in about 40nm. The HRTEM images confirmed that CdTe crystallite sizes were in the 2–4 nm range. The RGD shell was as thin as 0.5 nm, so the overall size of the CdTe-RGD probe was 3–5 nm. Most importantly, the obtained CdTe-RGD probe can be successfully applied to cancer cell imaging directly without going through any surface modification treatment.Furthermore, we improved the experimental formula and condition on the basis of CdTe-RGD QDs and successfully synthesized CdZnTe-RGD alloy QDs. The best quantum yield of CdZnTe QDs was above 56% and the minimum FWHM was about 36nm, the fluorescence intensity of which could be comparable with the typical mature CdTe-MPA QDs. The HRTEM images confirmed that the CdZnTe crystallite size was about 2-4nm. Cell experiment results showed that the cell imaging performance by CdZnTe-RGD alloy QDs was much better than CdTe-RGD QDs. Moreover, the toxicity of the QDs was reduced by mixing some Zn into the nanoparticles, which will be conducive to expanding the field of quantum dots in biological applications.