Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice.
Oncotarget
; 9(27): 18682-18697, 2018 Apr 10.
Article
en En
| MEDLINE
| ID: mdl-29721153
ABSTRACT
Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions. A tyrosine residue was added to the peptide to allow for 124I labeling and PET imaging. In a TNBC model in mice, systemic LinTT1-targeted polymersomes accumulated in early tumor lesions more than twice as efficiently as untargeted polymersomes with up to 20% ID/cc at 24 h after administration. The PET-imaging was very sensitive, allowing detection of tumors as small as â¼20 mm3. Confocal imaging of tumor tissue sections revealed a high degree of vascular exit and stromal penetration of LinTT1-targeted polymersomes and co-localization with tumor-associated macrophages. Our studies show that systemic LinTT1-targeted polymersomes can be potentially used for precision-guided tumor imaging and treatment of TNBC.
Texto completo:
1
Banco de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Oncotarget
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estonia