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)...

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.

A bis-BODIPY-based fluorescent probe (BODIPY-NN) is developed for Cu2+ detection in aqueous solutions and living cells. The sensing mechanism is based on the in situ generation of a benzimidazole–triazole receptor induced by Cu2+ ions.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been increasingly used as nanomedicine platforms due to their exceptional magnetic properties, which emerged from their nanoscopic sizes. Recently, SPIONs with a riboflavin (Rf)-citrate ligand were developed and showed increased internalization in breast cancer cells, with exceptional properties as T 2 contrast agents for magnetic resonance imaging (MRI). The interactions of the Rf-coated SPIONs with proteins from fetal bovine serum (FBS) were previously characterized to understand how the nanoparticles will interact with biomolecules. To closer mimic the human biological environments, human serum (HS) has been suggested as a better model. Therefore, in this work, protein coronas of bare, citrate-coated, and Rf-coated SPIONs formed with HS were studied by proteomic analysis to identify and quantify the nanoparticle–protein interaction. The results were compared with the FBS-derived coronas to understand the differences in the protein corona formation from different serum origins. Furthermore, the interactions of the SPIONs with riboflavin carrier protein (RCP), which is a target protein for the Rf-SPIONs, were also studied. The overall physical properties of the corona proteins were similar between the FBS and HS groups, but some specific homologous proteins interacted differently. The RCP was found to bind more to the citrate-coated SPIONs than the Rf-coated one. The outcome could be explained by molecular dynamics simulation, where the orientation of the Rf ligand did not favor the binding with RCP. The simulation results also showed the influence of surface hydrophilicity of the SPIONs on the RCP interaction. The combined data from proteomic and simulation analyses suggested a way to improve the Rf ligand to enhance the interaction with RCP and reduce the interactions with the serum proteins, which could enhance the specific cellular interactions and improve the Rf-SPIONs as MRI contrast agents for breast cancer.