Detection of small breast tumors using tumor penetrating-polymersomes engineered to target p 32 protein

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.