ABSTRACT
Background/
aim:
The overexpression of HER2 is correlated with poorer outcomes and
therapeutic resistance in
breast cancer patients. While HER2-targeted
therapies have shown improvement,
prognosis remains poor for HER2-positive
breast cancer patients, and these
treatments have limitations. Therefore, it is crucial to explore effective molecular
strategies for early
detection and
treatment of HER2-positive
breast cancers. Materials and
methods:
In this study, we employed the
cell-SELEX
method to generate a selective aptamer capable of recognizing HER2 in its native conformation within
breast cancer cells, for
theranostic applications. Utilizing an adherent
cell-SELEX approach, we developed and explored a
DNA aptamer, named HMAP7, which can specifically target HER2 in the MDA-MB-453 and SK-BR-3
human breast cancer cell lines. After sequencing, the binding affinities of 10 candidate aptamers to HER2 receptors were evaluated by measuring
fluorescence intensities within intact
cells using near-infrared
optical imaging. The
dissociation constant of HMAP7 was determined to be in the nanomolar range in both
cell lines.
Results:
The
cell-SELEX-derived aptamer sequence, HMAP7 (41-mer), exhibited the highest binding affinity and
specificity for HER2. HMAP7 was rapidly internalized into
breast cancer cells overexpressing HER2 but showed no uptake in the HER2 receptor-deficient
breast cancer cell line MDA-MB-231. Moreover, HMAP7 demonstrated remarkable selectivity for HER2, rendering it suitable for use in complex
biological systems.
Conclusions:
Our findings suggest that the novel
DNA aptamer HMAP7 holds promise for both
therapeutic and diagnostic applications, enabling selective delivery of
therapeutic agents or imaging of HER2-positive
breast tumors.