Photoimmunotheranostic agents for triple-negative breast cancer diagnosis and therapy that can be activated on demand.
Oncotarget
; 7(34): 54925-54936, 2016 Aug 23.
Article
in En
| MEDLINE
| ID: mdl-27448975
ABSTRACT
Triple-negative breast cancer (TNBC) is a heterogeneous disease in which the tumors do not express estrogen receptor (ER), progesterone receptor (PgR) or human epidermal growth factor receptor 2 (HER2). Classical receptor-targeted therapies such as tamoxifen or trastuzumab are therefore unsuitable and combinations of surgery, chemotherapy and/or radiotherapy are required. Photoimmunotheranostics is a minimally invasive approach in which antibodies deliver nontoxic photosensitizers that emit light to facilitate diagnosis and produce cytotoxic reactive oxygen species to induce apoptosis and/or necrosis in cancer cells. We developed a panel of photoimmunotheranostic agents against three TNBC-associated cell surface antigens. Antibodies against epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and chondroitin sulfate proteoglycan 4 (CSPG4) were conjugated to the highly potent near-infrared imaging agent/photosensitizer IRDye®700DX phthalocyanine using SNAP-tag technology achieving clear imaging in both breast cancer cell lines and human biopsies and highly potent phototherapeutic activity with IC50values of 62-165 nM against five different cell lines expressing different levels of EGFR, EpCAM and CSPG4. A combination of all three reagents increased the therapeutic activity against TNBC cells by up to 40%.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Photochemotherapy
/
Organosilicon Compounds
/
Immunoconjugates
/
Triple Negative Breast Neoplasms
/
Indoles
Type of study:
Diagnostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2016
Document type:
Article
Affiliation country:
Alemania