RT Journal Article
SR Electronic
T1 Detection of small breast tumors using tumor penetrating-polymersomes engineered to target p32 protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 187716
DO 10.1101/187716
A1 Lorena Simón-Gracia
A1 Pablo Scodeller
A1 Desirè Di Silvio
A1 Sergio Salazar
A1 Vanessa Gómez Vallejo
A1 Xabier Ríos
A1 Eneko San Sebastián
A1 Meina Suck
A1 Federica De Lorenzi
A1 Larissa Yokota Rizzo
A1 Saskia von Stillfried
A1 Kalle Kilk
A1 Twan Lammers
A1 Sergio E Moya
A1 Tambet Teesalu
YR 2017
UL http://biorxiv.org/content/early/2017/09/12/187716.abstract
AB Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The hyaluronic acid-binding p32 protein is overexpressed in TNBC, specifically in macrophages in hypoxic areas of the tumor. Here we used polyethylene glycol-polycaprolactone (PEG-PCL) polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for delivery of imaging and therapeutic payloads to TNBC lesions. A tyrosine residue was added to the peptide to allow for 124I labeling and PET imaging. Systemic LinTT1-targeted polymersomes accumulated in early tumor lesions more than twice as efficient 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 ∼20mm3. 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.