4.6 Article

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

Journal

NATURE BIOMEDICAL ENGINEERING
Volume 4, Issue 3, Pages 298-+

Publisher

NATURE RESEARCH
DOI: 10.1038/s41551-020-0528-7

Keywords

-

Funding

  1. NCATS NIH HHS [UL1 TR002345] Funding Source: Medline
  2. NCI NIH HHS [R01 CA171651, U54 CA199092, P50 CA094056, R50 CA211481, P30 CA091842] Funding Source: Medline
  3. NCRR NIH HHS [S10 RR031625] Funding Source: Medline
  4. NIBIB NIH HHS [R01 EB021048] Funding Source: Medline
  5. NIH HHS [S10 OD016237, S10 OD025264, S10 OD027042, S10 OD020129] Funding Source: Medline

Ask authors/readers for more resources

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. A cyclic octapeptide labelled with a near-infrared dye and that binds, with high affinity at high levels of calcium, to phosphorylated protein Annexin A2 in a range of solid tumours, serves as a tumour-selective imaging probe.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available