Detection of small breast tumors using tumor penetrating-polymersomes engineered to target p32 protein
bioRxiv(2018)
摘要
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.
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关键词
PET,tumor-penetrating peptide,polymersomes,triple negative breast cancer,p32
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