Anti-CEA tagged iron nanoparticles for targeting triple-negative breast cancer

Abstract

Systemic therapy is generally required for breast cancer. However, treatment toxicity and side effects are a concern, especially for triple-negative breast cancer (TNBC), a subtype that usually develops resistance to chemotherapy. To overcome this issue, new nanoformulations capable of targeting cancer cells have been developed and alternative biomarkers have been explored as target molecules for TNBC management. In this study, we performed an in vivo assay in a murine orthotopic TNBC model to evaluate the targeting ability of anti-carcinoembryonic antigen (anti-CEA) loaded nanoparticles (labelled MFCEA), which had been previously synthetized by our research group. 4T1 cells were injected in the mammary gland of balb-c mice, and tumors were evaluated for CEA expression by immunohistochemistry. Tumor-bearing mice received targeted (MFCEA) and non-targeted (MF) nanoparticles intraperitoneally. Tumors were removed 1, 4, 15 and 24 h after treatment, and Prussian blue iron staining was performed. Our results showed, as far as we know for the first time, that 4T1 induced tumors are CEA positive, and this opens up new prospects for treating TNBC. Furthermore, MFCEA nanoparticles were able to target malignant tissue and were retained in the tumor for longer than MF nanoparticles. The retention property of MFCEA, together with the absence of toxicity observed in the MTT assay, make these nanoparticles a promising device for management of CEA positive tumors and perhaps for TNBC. Nevertheless, further studies must be carried out to improve their performance and ensure safety for clinical studies.

Glycans as Targets for Drug Delivery in Cancer

“…Some other studies have employed methods to evaluate CEA, a cell surface glycoprotein overexpressed in several tumors, as a therapeutic target. A strategy was created for the targeting of triple-negative breast cancer using CEA-directed iron NPs, which depicted an enhanced tumor targeting capacity [ 120 ]. Additionally, CEA-targeting PLGA-PEG NPs loaded with paclitaxel have been demonstrated to selectively bind and trigger the death of CEA-expressing colorectal cancer cells [ 121 ].…”