Novel Iodine nanoparticles target vascular mimicry in intracerebral triple negative human MDA-MB-231 breast tumors

Abstract

Triple negative breast cancer (TNBC), ~ 10–20% of diagnosed breast cancers, metastasizes to brain, lungs, liver. Iodine nanoparticle (INP) radioenhancers specifically localize to human TNBC MDA-MB-231 tumors growing in mouse brains after iv injection, significantly extending survival of mice after radiation therapy (RT). A prominent rim of INP contrast (MicroCT) previously seen in subcutaneous tumors but not intracerebral gliomas, provide calculated X-ray dose-enhancements up to > eightfold. Here, MDA-MB-231-cells, INPs, CD31 were examined by fluorescence confocal microscopy. Most INP staining co-localized with CD31 in the tumor center and periphery. Greatest INP/CD31 staining was in the tumor periphery, the region of increased MicroCT contrast. Tumor cells are seen to line irregularly-shaped spaces (ISS) with INP, CD31 staining very close to or on the tumor cell surface and PAS stain on their boundary and may represent a unique form of CD31-expressing vascular mimicry in intracerebral 231-tumors. INP/CD31 co-staining is also seen around ISS formed around tumor cells migrating on CD31+ blood-vessels. The significant radiation dose enhancement to the prolific collagen I containing, INP-binding ISS found throughout the tumor but concentrated in the tumor rim, may contribute significantly to the life extensions observed after INP-RT; VM could represent a new drug/NP, particularly INP, tumor-homing target.

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray

“…These nanoparticles have prolonged blood half-life and exhibited enhancement of radiation therapy in animal model systems 22 . A recent report shows that these nanoparticles bind collagen I mediated by PEG 42 and thus they appear to differ from the nanoparticles we developed in terms of its material and the mode of action. Various types of iodine-containing nanoparticles are expected to be developed in the future.…”

Iodine Nanoparticles (Niodx™) for Radiotherapy Enhancement of Glioblastoma and Other Cancers: An NCI Nanotechnology Characterization Laboratory Study

“…No endothelial cells are present, and black spaces surrounded by tumor cells (red) are vascular channels formed by the tumor cells mimicking endothelial cells. Niodx shows strong binding to these channels [ 37 ]. Bar = 20 μm.…”

“…For example, coating nanoparticles with gallic acid (probably self-polymerized) was recently shown to increase binding to orthotopic GL261 gliomas in mice from 3.6% ID/g to 13.5% (3.75-fold) compared to PEG coated NPs [ 36 ]. For Niodx, an interesting interaction was discovered where the iodine nanoparticle specifically bound to human triple negative breast cancer (TNBC) tumors growing in the brains of athymic mice [ 37 ]. This specific binding increased iodine loading concentrations from about 1% iodine for U87 gliomas to 3% (average tumor concentration at the growing edge) for the 231 TNBC growing in the mouse brain [ 11 , 27 ].…”

“…Interestingly, in this breast to brain metastasis model, there was an abundance of vascular mimicry typified by irregularly shaped spaces (ISS [ 37 ]) instead of normal, more circular endothelial cell-lined tumor vessels (cf. Figure 12 ).…”

SLFN12 Over-expression Sensitizes Triple Negative Breast Cancer Cells to Chemotherapy Drugs and Radiotherapy

“…We hypothesized that over-expression of SLFN12 would sensitize TNBC cells to specific chemotherapy and radiotherapy treatments. To test this hypothesis, we used MDA-MB-231 cells, which are a common model for TNBC (16). An MDA-MB-231 subclone that stably over-expresses SLFN12 (denoted LV) was compared to another subclone that had been transfected with an empty vector virus and therefore, expressed only baseline levels of SLFN12, denoted EV (4).…”