Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2

Duanwen Shen, Baogang Xu, Kexian Liang, Rui Tang, Gail P. Sudlow, Christopher Egbulefu, Kevin Guo, Avik Som, Rebecca Gilson, Dolonchampa Maji, Suman Mondal, Le Moyne Habimana-Griffin, Walter J. Akers, Shunqiang Li, Yang Liu, Sharon Bloch, Sid Kurkure, Zohar Nussinov, Alexander Seidel, Shaw Wei D. TsenSamuel Achilefu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The heterogeneity and continuous genetic adaptation of tumours complicate their detection and treatment via the targeting of genetic mutations. However, hallmarks of cancer such as aberrant protein phosphorylation and calcium-mediated cell signalling provide broadly conserved molecular targets. Here, we show that, for a range of solid tumours, a cyclic octapeptide labelled with a near-infrared dye selectively binds to phosphorylated Annexin A2 (pANXA2), with high affinity at high levels of calcium. Because of cancer-cell-induced pANXA2 expression in tumour-associated stromal cells, the octapeptide preferentially binds to the invasive edges of tumours and then traffics within macrophages to the tumour’s necrotic core. As proof-of-concept applications, we used the octapeptide to detect tumour xenografts and metastatic lesions, and to perform fluorescence-guided surgical tumour resection, in mice. Our findings suggest that high levels of pANXA2 in association with elevated calcium are present in the microenvironment of most solid cancers. The octapeptide might be broadly useful for selective tumour imaging and for delivering drugs to the edges and to the core of solid tumours.

Original languageEnglish
Pages (from-to)298-313
Number of pages16
JournalNature Biomedical Engineering
Volume4
Issue number3
DOIs
StatePublished - Mar 1 2020

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