br The recruitment of ZH endows the Qdot conjugated
The recruitment of ZH2 endows the Qdot-conjugated peptide with the ability for selective imaging of HER2/neu-positive breast cancer Cyclosporin H (Fig. 3(B)). ZH2 is a bivalent anti-HER2/neu a body. The a body molecule is an antibody mimic while it is small and displays a high a nity to the target protein. NPs, liposomes or DNAs have been conjugated anti-HER2/neu a body for selective delivery of the drug and the gene cargo [41–43]. In our previ-ous study, an invasive E. coli strain was constructed with ZH2 displayed on its surface . The strain was specifically internal-ized into breast cancer cells with high e ciency. Equipped with the lycopene synthesis machinery, the ZH2-displayed E. coli strain
Fig. 5. Treatment of cancer cells by Qdot-MNP conjugate. (A) Analysis of the MNP-based conjugates by fluorescence microscopy. Two MNP-based conjugates were in-dividually isolated by a magnet. The fluorescence image of peptide-MNP (left) and of Qdot-MNP conjugate (right) were analyzed by fluorescence microscopy. (B) Cell imagining by Qdot-MNP conjugate. Cancer cells were administrated with either Qdot-MNP conjugate or peptide-MNP. The inset showed the image of the Qdot-MNP conjugate-treated SKBR3 cell with stained nucleus (blue) and Qdot-emitted fluorescence (red). Keys: (1) control cell with Qdot-MNP conjugate; (2) HER2/neu-positive cell without treatment; (3) HER2/neu-positive cell with peptide-MNP; (4) HER2/neu-positive cell with Qdot-MNP conjugate. (For interpretation of the refer-ences to color in this figure legend, the reader is referred to the web version of this article.)
enabled to suppress the growth of HER2/neu-positive breast can-cer cells . The internalization of the ZH2-borne peptide pro-ceeded in a time dependent manner (Fig. 4), which is consistent with the previous report on the anti-HER2/neu a body-mediated invasion kinetics for the conjugated materials . It is recognized that the translocation path initiates with the endocytic internaliza-tion of HER2/neu receptor which travels to the nucleus after inter-acting with the nuclear pore protein . It is likely that the ZH2-borne peptide enters the same transport route, and the entry ma-chinery fails to function in the fixed cell which loses the metabolic activity (Fig. 3(B)). This view is further supported by the observa-tion of internalized peptides scattering around the nucleus of cells (Fig. 3(B)).
In summary, the combined use of Qdot and MNP is highly use-ful for many biological applications. It has been a research focus on the development of biosensing devices in the healthcare, food, and environment field . This study turns to highlight useful-ness of the Qdot- and MNP-conjugated peptide for simultaneous cell imagining and therapy. The result illustrates the general appli-cation of the functionalized peptide for HER2/neu-positive breast cancer cells (i.e. MCF-7/her18 and SKBR3). Equipped with the func-tional ZH2, the Qdot-conjugated peptide elicits excellent staining of breast cancer cells expressing HER2/neu. The potential of this ap-proach is to develop an advanced bioassay for early detection of cancers. The ZH2-borne peptide with the Qdot conjugate is easily isolated by a magnet and then coupled with the MNP-conjugated peptide to perform hyperthermia. To achieve optimum therapeutic
e cacy, this peptide-based conjugate system is simple and flexi-ble for tuning various modules such as the protein-protein interac-tion domains for lowering the immunogenicity, the targeting motif for specific recognition of various biomarkers, and the biotinyla-tion site for the packing density of specialized NPs. Future work is required for the evaluation of the theranostic application by the developed bioconjugate system in vivo.
The authors declare that they have no competing interests.
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