In:
Journal of Nanobiotechnology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-05-25)
Abstract:
Triple-negative breast cancer (TNBC) is more prone to distant metastasis and visceral recurrence in comparison to other breast cancer subtypes, and is related to dismal prognosis. Nevertheless, TNBC has an undesirable response to targeted therapies. Therefore, to tackle the huge challenges in the diagnosis and treatment of TNBC, Nectin-4 was selected as a theranostic target because it was recently found to be highly expressed in TNBC. We developed anti-Nectin-4 monoclonal antibody (mAb Nectin-4 )-based theranostic pair, 99m Tc-HYNIC-mAb Nectin-4 and mAb Nectin-4 -ICG. 99m Tc-HYNIC-mAb Nectin-4 was applied to conduct immuno-single photon emission computed tomography (SPECT) for TNBC diagnosis and classification, and mAb Nectin-4 -ICG to mediate photothermal therapy (PTT) for relieving TNBC tumor growth. Methods Nectin-4 expression levels of breast cancer cells (MDA-MB-468: TNBC cells; and MCF-7, non-TNBC cells) were proved by western blot, flow cytometry, and immunofluorescence imagning. Cell uptake assays, SPECT imaging, and biodistribution were performed to evaluate Nectin-4 targeting of 99m Tc-HYNIC-mAb Nectin-4 . A photothermal agent (PTA) mAb Nectin-4 -ICG was generated and characterized. In vitro photothermal therapy (PTT) mediated by mAb Nectin-4 -ICG was conducted under an 808 nm laser. Fluorescence (FL) imaging was performed for mAb Nectin-4 -ICG mapping in vivo. In vivo PTT treatment effects on TNBC tumors and corresponding systematic toxicity were evaluated. Results Nectin-4 is overexpressed in MDA-MB-468 TNBC cells, which could specifically uptake 99m Tc-HYNIC-mAb Nectin-4 with high targeting in vitro . The corresponding immunoSPECT imaging demonstrated exceptional performance in TNBC diagnosis and molecular classification. mAb Nectin-4 -ICG exhibited favourable biocompatibility, photothermal effects, and Nectin-4 targeting. FL imaging mapped biodistribution of mAb Nectin-4 -ICG with excellent tumor-targeting and retention in vivo. Moreover, mAb Nectin-4 -ICG-mediated PTT provided advanced TNBC tumor destruction efficiency with low systematic toxicity. Conclusion mAb Nectin-4 -based radioimmunoimaging provides visualization tools for the stratification and diagnosis for TNBC, and the corresponding mAb Nectin-4 -mediated PTT shows a powerful anti-tumor effect. Our findings demonstrate that this Nectin-4 targeting strategy offers a simple theranostic platform for TNBC.
Type of Medium:
Online Resource
ISSN:
1477-3155
DOI:
10.1186/s12951-022-01444-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2100022-0
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