A PEG-assisted membrane coating to prepare biomimetic mesoporous silicon for PET/CT imaging of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) diagnosis remains challenging without expressing critical receptors. Cancer cell membrane (CCm) coating has been extensively studied for targeted cancer diagnostics due to attractive features such as good biocompatibility and homotypic tumor-targeting. However, the present study found that widely used CCm coating approaches, such as extrusion, were not applicable for functionalizing irregularly shaped nanoparticles (NPs), such as porous silicon (PSi). To tackle this challenge, we proposed a novel approach that employs polyethylene glycol (PEG)-assisted membrane coating, wherein PEG and CCm are respectively functionalized on PSi NPs through chemical conjugation and physical absorption. Meanwhile, the PSi NPs were grafted with the bisphosphonate (BP) molecules for radiolabeling. Thanks to the good chelating ability of BP and homotypic tumor targeting of cancer CCm coating, a novel PSi-based contrast agent (CCm-PEG-89Zr-BP-PSi) was developed for targeted positron emission tomography (PET)/computed tomography (CT) imaging of TNBC. The novel imaging agent showed good radiochemical purity (∼99 %) and stability (∼95 % in PBS and ∼99 % in cell medium after 48 h). Furthermore, the CCm-PEG-89Zr-BP-PSi NPs had efficient homotypic targeting ability in vitro and in vivo for TNBC. These findings demonstrate a versatile biomimetic coating method to prepare novel NPs for tumor-targeted diagnosis.

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

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.