Original Article
A multifunctional peptide for targeted imaging and chemotherapy for nasopharyngeal and breast cancers

https://doi.org/10.1016/j.nano.2015.03.011Get rights and content

Abstract

The L-peptide plays a role as a universal ligand binding specifically to nasopharyngeal carcinoma (NPC) and other cancers but not normal cells. It was used to link iron oxide nanoparticles, and injected intravenously to SCID mice bearing NPC and breast cancer xenografts for MR analysis, and showed significant change of MR signal intensity in the xenograft regions. Using this conjugate as a ligand to localize the L-peptide targeted protein in the cancer surgical specimens, a clear reaction product was identified in the tumor cells of both cancer types. If the L-peptide-linked-liposomal doxorubicin was used to treat the SCID mice bearing other NPC or breast cancer xenograft, a high efficacy of chemotherapy with minimal adverse effect was observed. In conclusion, the L-peptide has a considerable potential for clinical usage for targeted imaging, peptide histochemical localization of targeted protein, and targeted chemotherapy for different cancer types.

From the Clinical Editor

Targeted chemotherapy to cancer cells will enable maximum drug delivery but minimal systemic side effects. In this article, the authors identified a protein, L-peptide, on tumor cells. They also subsequently confirmed the specificity of this protein in animal experiments using iron oxide nanoparticles. The discovery of this marker could lead to future development of better chemotherapy.

Graphical abstract

A. The pegylated L-peptide N-terminal was linked to dextran iron oxide nanoparticle (L-P-Dex-Fe3O4), then reacted with L-peptide binding protein on the cancer cell surface and subjected to Prussian blue reaction.

B. The pegylated N-terminal of L-peptide was linked to the liposomal doxorubicin (L-P-L-D), and then the C-terminal of the L-peptide could bind to the L-peptide binding protein on the cancer cell surface, resulting in ingestion of the liposomal doxrubicin by the tumor cells.

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Section snippets

Methods

Cell lines, biopsy and surgical specimens, animals, peptides

For details, please see the supplementary methods.

Flow cytometry analysis of L-peptide binding cells in NPC and other cancer cell lines by FITC-L-peptide

For details, please see the supplementary methods.

Localization of the L-peptide-targeted protein in NPC and breast cancer cell lines and their surgical specimens.

For details, please see the supplementary methods.

Localization of L-peptide targeted protein by L-phage

For details, please

Flow cytometry analysis of the L-peptide binding cells in different cancer cell lines

When the NPC-TW07 line was incubated with the FITC-L-P, a clear peak was found in the histogram (Figure 1, A). It is significantly different from NPC cells incubated with FITC-C-P. When other NPC lines including NPC-TW01 and other cancer lines including NSCLC (A549 and H1299 cell line), neuroblastoma (Be2C), and breast cancer (MDA-MB157) were incubated with the FITC-L-P, all showed a clear binding peak that was different from the immortalized renal cell line (293 T cell) (Figure 1, B). A

Discussion

In our present experiment, we found 7 different cancer cell lines, including the NPC lines (TW01 and TW07), non-small-cell lung cancer lines (A549 and H1299), neuroblastoma line (Be2C) and breast cancer line (MB157), all showed specific binding ability by FITC-L-peptide. However, the immortalized embryonic renal epithelial line (293 T) revealed very weak or no binding activity (Figure 1, B, D).These data suggest that L-P can specifically bind to NPC and other cancer cell lines, but not the

Acknowledgements

We thank 7 T animal MRI Core Lab of the Neurobiology and Cognitive Science Center for technical and facility supports, and CH Hsieh and JH Chen of Instrumentation Center for MRI experiments at National Taiwan University.

References (19)

There are more references available in the full text version of this article.

Role of funding source: This study was supported in part by a research grant from National Taiwan University Hospital (NTUH 99-A102 to CTL and JKH), and by the grants from National Science Council (NSC97-2323-B-002-004, NSC100-2325-B-002-034, NSC101-2325-B-002-030 and NSC102-2325-B-002-029 to CTL; and NSC97-2314-B-303-018 MY 2 to JKH).

Competing interests: There are no competing interests to report.

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Present address: Department of Medical Imaging, Tzu-Chi General Hospital, Taipei Branch, Taipei 231, Taiwan.

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