Mullen, N. | bioRxiv Science

bioRxiv2024

Adrenocortical Cancer Cell uptake of Iron Oxide Nanoparticles

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis, treated primarily through surgery and chemotherapy. Other treatments like radiation or thermal ablation for metastases have limited success, and recurrence is common. More effective management options are needed. Magnetic iron oxide nanoparticles (IONP) show promise in cancer treatment due to their ability to be modified for selective uptake by cancer cells. This study investigated IONP uptake in ACC cell lines (H295R, HAC-15, MUC-1) using a multicellular model with endothelial cells (HUVEC) and monocytes. IONP uptake was concentration- and time-dependent, with optimal uptake at 10 {micro}g/mL. IONP were found in the cytoplasm and intracellular vesicles of ACC cells. However, endothelial cells and monocytes also absorbed IONP, reducing uptake by ACC cells. These findings suggest ACC cells actively take up IONP, but better targeting is needed to enhance uptake specificity and efficiency.

pharmacology and toxicology↗

bioRxiv2024

Characterization of a Biochemical Mouse Model of Primary Aldosteronism for Thermal Therapies

IntroductionAldosterone-producing adenoma (APA) is the most common cause of endocrine-related hypertension but surgery is not always feasible. Current medical interventions are associated with significant side effects and poor patient compliance. New APA animal models that replicate basic characteristics of APA and give physical and biochemical feedback are needed to test new non-surgical treatment methods, such as image-guided thermal ablation, MethodsA model of APA was developed in nude mice using HAC15 cells, a human adrenal carcinoma cell line. Tumor growth, aldosterone production, and sensitivity to angiotensin II were characterized in the model. The utility of the model was validated via treatment with microwave ablation and characterization of the resulting physical and biochemical changes in the tumor. ResultsThe APA model showed rapid and relatively homogeneous growth. The tumors produced aldosterone and steroid precursors in response to angiotensin II challenge, and plasma aldosterone levels were significantly higher in tumor bearing mice two hours after challenge verses non-tumor bearing mice. The model was useful for testing microwave ablation therapy, reducing aldosterone production by 80% in treated mice. ConclusionThe HAC15 model is a useful tumor model to study and develop localized treatment methods for APA.

cancer biology↗