Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice.

TitleApplication of polymersomes engineered to target p32 protein for detection of small breast tumors in mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsSimón-Gracia L, Scodeller P, Fuentes SSalazar, Vallejo VGómez, Ríos X, San Sebastián E, Sidorenko V, Di Silvio D, Suck M, De Lorenzi F, Rizzo LYokota, von Stillfried S, Kilk K, Lammers T, Moya SE, Teesalu T
JournalOncotarget
Volume9
Issue27
Pagination18682-18697
Date Published2018 Apr 10
ISSN1949-2553
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 I 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 ∼20 mm. 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.

DOI10.18632/oncotarget.24588
Alternate JournalOncotarget
PubMed ID29721153
PubMed Central IDPMC5922347
Grant List / / Wellcome Trust / United Kingdom