Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice
Lorena Simón-Gracia1, Pablo Scodeller1, Sergio Salazar Fuentes2
1Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
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 ∼20 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.
Insights
Targeted polymersomes effectively image triple negative breast cancer (TNBC) lesions. This novel approach enhances early detection and precision treatment of this aggressive cancer.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple negative breast cancer (TNBC) is an aggressive subtype requiring early diagnosis and targeted therapies.
- The protein p32 is overexpressed on malignant cells and in the tumor microenvironment of TNBC.
- Targeted delivery systems are crucial for improving diagnostic and therapeutic efficacy in TNBC.
Purpose of the Study:
- To develop and evaluate p32-targeted polymersomes for enhanced imaging of TNBC.
- To assess the accumulation and penetration of targeted polymersomes in a TNBC mouse model.
- To determine the sensitivity of PET imaging using these targeted nanocarriers.
Main Methods:
- Construction of polyethylene glycol-polycaprolactone polymersomes.
- Affinity targeting of polymersomes with the p32-binding peptide LinTT1.
- 124I labeling for Positron Emission Tomography (PET) imaging in a TNBC mouse model.
- Confocal imaging of tumor tissue sections to assess vascular exit and stromal penetration.
Main Results:
- LinTT1-targeted polymersomes showed more than twofold increased accumulation in early TNBC lesions compared to untargeted ones.
- PET imaging enabled sensitive detection of small tumors (∼20 mm3).
- Targeted polymersomes demonstrated significant vascular exit, stromal penetration, and co-localization with tumor-associated macrophages.
Conclusions:
- Systemic administration of LinTT1-targeted polymersomes facilitates precise imaging of TNBC.
- This nanotechnology holds potential for precision-guided tumor imaging and future therapeutic applications in TNBC.
- The study highlights the utility of targeting p32 for early and sensitive detection of TNBC.
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