High‐Contrast Magnetic Resonance Imaging and Efficient Delivery of an Albumin Nanotheranostic in Triple‐Negative Breast Cancer Xenografts

Abstract

Triple-negative breast cancer (TNBC) is a fast growing and strong metastasizing tumor, which presents almost no cellular receptors that can be addressed by targeted therapeutics. In addition, TNBC is often characterized by high tumor grading, fast growth rates, and early metastasis. Therefore, multifunctional drug carriers allowing efficient drug delivery and bioimaging to treat and track TNBC tissue in vivo would be highly desirable. A human serum albumin-based polyethylene glycol copolymer (dcHSA-Gd-Dox) is synthesized combining multiple copies of the chemotherapeutic drug doxorubicin and gadolinium (III) (Gd(III))-based magnetic resonance imaging (MRI) contrast agent. The biodegradable albumin-based nanocarriers reveal high-contrast tumor imaging and efficient drug delivery in a preclinical TNBC xenograft model, where the xenografts are grown on the chorioallantoic membrane of fertilized chick eggs. dcHSA-Gd-Dox is injected intravenously, and the distribution of the compound is monitored by MRI and inductively coupled optical plasma emission spectrometry. dcHSA-Gd-Dox is rapidly taken up into MDA-MB-231 cells and exhibits significant cytotoxic efficacy. dcHSA-Gd-Dox combines high tissue enrichment with low systemic toxicity and high-contrast MRI rendering it an attractive nanotheranostic for TNBC.

Tumor grafted – chick chorioallantoic membrane as an alternative model for biological cancer research and conventional/nanomaterial-based theranostics evaluation

“…Meanwhile, the nanoencapsulation of doxorubicin improved the overall survival rate of the embryos compared to the models treated with doxorubicin in free solution. Attenuated cancer cell proliferation and enhanced apoptosis were also observed on NPtreated tumor xenografts [160].…”

“…Slices of fixed tumor can be processed as for immunohistochemistry, and biomolecules specifically present in certain cell types or under a particular condition can be identified using reagents tagged with fluorescent probes. Some of these commonly utilized fluorophoretagged or probe-detected biomarkers include desmin for the vascularization [132], vimentin for stromal cells [156], Ki67 for proliferation [44], terminal deoxynucleotidyl transferase (Tdt)mediated dUTP nick-end labeling (TUNEL) for DNA fragmentation [160], tumor type-specific antibodies [49,92,138], or avian-specific markers [131]. Meanwhile, blood vessels can be visualized using fluorophore-conjugated dextran [169].…”

“…To further facilitate the localization of fluorescent materials within a tumor mass, cells can be incubated with fluorescent organelle markers for simultaneous visualization [125]. Otherwise, cells can be genetically engineered prior to grafting such that they express reporter molecules like GFP and firefly luciferase that are detectable via fluorescence or luminescence [11,96,156,160]. Bioluminescence imaging (BLI) can then enable specific detection and quantitative monitoring of the engineered tumors over the course of the CAM assay (Figure 4(e)) [11,96].…”

“…In certain cases, technologies evaluated on CAM tumor models are specifically developed for tumor imaging. Thus, tumor growth and other features of the embryo are monitored and visualized, for instance using MRI [140,160], MRI/PET [97], and PET/CT [98] (Figure 3).…”

Bardoxolone-Methyl (CDDO-Me) impairs tumor growth and radioresistance of oral squamous cell carcinoma (OSCC) cells via accumulation of reactive oxygen species

“…The chick egg chorioallantoic membrane (CAM) tumor model was used as previously described (16)(17)(18). Brie y, fertilized chicken eggs were incubated at 37 °C and 60% relative air moisture for 7 days before fenestration and placement of a silicone ring (diameter 5 mm) on the vascularized CAM.…”