Breast cancer accounts up to 10% of the newly diagnosed cancer cases worldwide, making it the most common cancer found in women. The use of superparamagnetic iron oxide nanoparticles (SPIONs)...

No abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the most beneficial tools for biomedicine, especially in theranostic applications. Even though SPIONs have excellent properties regarding their biocompatibility and unique magnetic properties, they lack stability in biological fluids. To stabilize and increase the specificity of the SPIONs to target desirable cells or tissues, several surface coatings have been introduced. These surface coatings can lead to different preferences of serum protein bindings, which ultimately determine their behaviors in vitro and in vivo. Thus, understanding the interaction of SPIONs with biological systems is important for their biocompatible design and clinical applications. In this study, using proteomic analyses, we analyzed the protein corona fingerprints on SPIONs with two different coatings, including citrate and riboflavin, that have been widely used as surface coatings and ligands for enhancing cellular uptake in breast cancer cells. Though both citrate-coated SPIONs (C-SPIONs) and riboflavin-coated SPIONs (Rf-SPIONs) showed similar sizes and zeta potentials, we found that Rf-SPIONs adsorbed more serum proteins than bare SPIONs (B-SPIONs) or C-SPIONs, which was likely due to the higher hydrophobicity of the riboflavin. The enriched proteins consisted mainly of immune-responsive and blood coagulation proteins with different fingerprint profiles. Cellular uptake studies in MCF-7 breast cancer cells comparing the activities of preformed and in situ coronas showed different uptake behaviors, suggesting the role of protein corona formation in promoting the interaction between the SPIONs and the cells. The results obtained here provide the essential information for further development of the potential strategy to reduce or stimulate immune response in vivo to increase therapeutic applications of both C-SPIONs and Rf-SPIONs.

Combating triple-negative breast cancer (TNBC) is one of the greatest challenges in cancer therapy. This is primarily due to the difficulties in developing drug delivery systems that can effectively target cancer sites. In this study, we demonstrated a proof-of-principle concept using modified surfaces of poly(lactic-co-glycolic acid) nanoparticles linked with a riboflavin analogue (PLGA-CSRf) to obtain a dualfunctional material. PLGA-CSRf nanoparticles were able to function as a drug delivery ligand and a photodynamic therapy agent for TNBC cells (MDA-MB-231). Biocompatibility of novel PLGA-CSRf nanoparticles was evaluated with both breast cancer and normal breast (MCF-10A) cells. In vitro studies revealed a six-fold increase in the cellular uptake of PLGA-CSRf nanoparticles in cancer cells compared with normal cells. The results demonstrate the ability of riboflavin (Rf) to enhance the delivery of PLGA nanoparticles to TNBC cells. The viability of TNBC cells was decreased following treatment with doxorubicin-encapsulated PLGA-CSRf nanoparticles in combination with UV irradiation, due to the photosensitizing property of Rf on the surface of the nanoparticles. This work demonstrated the ability of PLGA-CSRf to function both as an effective drug delivery carrier and as a therapeutic entity, with the potential to enhance photodynamic effects in the highly aggressive TNBC model.