Breast cancer accounts for 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) has been beneficial in the advancement of contrast agents and magnetic hyperthermia (MH) for the diagnosis and treatment of cancers. To achieve delivery of SPIONs to cancer cells, surface functionalization with specific ligands are required. Riboflavin carrier protein (RCP) has been identified as an alternative target for breast cancer cells. Here, we report a novel riboflavin (Rf)-based ligand that provides SPIONs with enhanced colloidal stability and high uptake potential in breast cancer cells. This is achieved by synthesizing an Rf-citrate ligand. The ligand was tested in a multicore SPION system, and affinity to RCP was assessed by isothermal titration calorimetry which showed a specific, entropy-driven binding. MRI and MH responses of the coated Rf-SPIONs were tested to evaluate the suitability of this system as a theranostic platform. Finally, interaction of the Rf-SPIONs with breast cancer cells was evaluated by in vitro cellular uptake in MCF-7 breast cancer cells. The overall characterization of the Rf-SPIONs highlighted the excellent performance of this platform for theranostic applications in breast cancer.
Nearly four million yearly deaths can be attributed to respiratory diseases, prompting a huge worldwide health emergency. Additionally, the COVID-19 pandemic’s death toll has surpassed six million, significantly increasing respiratory disease morbidity and mortality rates. Despite recent advances, it is still challenging for many drugs to be homogeneously distributed throughout the lungs, and specifically to reach the lower respiratory tract with an accurate sustained dose and minimal systemic side effects. Engineered nanocarriers can provide increased therapeutic efficacy while lessening potential biochemical adverse reactions. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, has attracted significant interest as an inhalable drug delivery system. However, the influence of the nanocarrier surface charge and its intratracheal instillation has not been addressed so far. In this study, we fabricated red fluorescent PLGA nanocapsules (NCs)—Cy5/PLGA—with either positive (Cy5/PLGA+) or negative surface charge (Cy5/PLGA-). We report here on their excellent colloidal stability in culture and biological media, and after cryo-storage. Their lack of cytotoxicity in two relevant lung cell types, even for concentrations as high as 10 mg/mL, is also reported. More importantly, differences in the NCs’ cell uptake rates and internalization capacity were identified. The uptake of the anionic system was faster and in much higher amounts—10-fold and 2.5-fold in macrophages and epithelial alveolar cells, respectively. The in vivo study demonstrated that anionic PLGA NCs were retained in all lung lobules after 1 h of being intratracheally instilled, and were found to accumulate in lung macrophages after 24 h, making those nanocarriers especially suitable as a pulmonary immunomodulatory delivery system with a marked translational character.