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Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release

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Abstract

Peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome. Here we show the formation of tryptophan–phenylalanine dipeptide nanoparticles (DNPs) that can shift the peptide's intrinsic fluorescent signal from the ultraviolet to the visible range. The visible emission signal allows the DNPs to act as imaging and sensing probes. The peptide design is inspired by the red shift seen in the yellow fluorescent protein that results from ππ stacking and by the enhanced fluorescence intensity seen in the green fluorescent protein mutant, BFPms1, which results from the structure rigidification by Zn(II). We show that DNPs are photostable, biocompatible and have a narrow emission bandwidth and visible fluorescence properties. DNPs functionalized with the MUC1 aptamer and doxorubicin can target cancer cells and can be used to image and monitor drug release in real time.

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Figure 1: Design of the self-assembled fluorescent DNPs through bioinspiration by the molecular principles that underlie the GFP family.
Figure 2: Optical characterizations of the DNPs.
Figure 3: Comparison of the DNPs with the organic dye Rh6G and QDs.
Figure 4: DNPs modified with the MUC1 aptamer target A549 human carcinoma epithelial cells.
Figure 5: Fluorescence monitoring of DOX loading and releasing from the DNPs.

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Acknowledgements

This research is sponsored by the National Science Foundation (CMMI: 1437177). The authors are grateful for the support.

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Contributions

Z.F. and M.Z. conceived and designed the experiments, Z.F., L.S., Y.H. and Y.W. performed the experiments, all the co-authors analysed the data, M.Z. contributed the materials and analysis tools, and Z.F. and M.Z. co-wrote the paper.

Corresponding author

Correspondence to Mingjun Zhang.

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The authors declare no competing financial interests.

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Fan, Z., Sun, L., Huang, Y. et al. Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release. Nature Nanotech 11, 388–394 (2016). https://doi.org/10.1038/nnano.2015.312

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