Design of a magnetic nanocarrier containing phyllacanthone as delivery of anticancer phytochemical: Characterization and theranostic in vitro applications

Cancer is a complex and multifactorial disease that remains one of the greatest challenges for modern medicine. High mortality rates and increasing global incidence drive the search for new therapeutic strategies. Medicinal plants are essential in this context, as they are rich sources of bioactive compounds with relevant pharmacological properties, including anticancer effects. Among these compounds, phyllacanthone (PHY) stands out, a terpene isolated from the species Cnidoscolus quercifolius, widely distributed in several regions of Brazil. PHY demonstrated significant antitumor activity, especially against human melanoma and lung cancer, suggesting its potential as a therapeutic agent in oncological treatment. However, limitations such as low aqueous solubility and volatility compromise the efficacy of PHY, requiring the development of drug delivery systems. The encapsulation of bioactive molecules in nanocarriers emerges as a promising approach to overcome these barriers, improve therapeutic efficacy, and minimize possible adverse effects. Given this scenario, the present study aimed to develop magnetic iron oxide nanoparticles (MIONPs) coated with β-cyclodextrin (β-CD) to load PHY efficiently. The resulting system (Fe₃O₄@βCD-PHY) was designed for combined therapeutic applications involving thermal and chemical therapy and for diagnostic imaging, exploring its potential as a contrast agent in modalities such as photoacoustic and magnetic resonance imaging (MRI). The nanocarrier was prepared using the coprecipitation method and characterized by several techniques. TEM, DLS, and zeta potential analyses revealed the presence of spherical nanoparticles, with an average size of 15 nm in diameter and a potential of -20.7 mV at pH 5. The PHY loading efficiency study showed a rate higher than 60%, with more than 70% of release capacity at acidic pH. Regarding the application in imaging diagnosis, the nanocomposite showed potential as T2 contrast agents in MRI, registering a value of r2 = 127,034 mM⁻¹s⁻¹ under a magnetic field of 1.4 T. Photoacoustic imaging tests showed robust signals in the second biological window (1064 nm) and, in biological tissues, it was possible to obtain images with good resolution up to a depth of 5 mm. Additionally, magnetic hyperthermia studies have indicated significant heating efficiency, reaching therapeutic temperatures at conditions well below the permitted limit of field strength and frequency reported for safe application. Finally, Fe₃O₄@βCD loaded with PHY exhibited enhanced cytotoxic effects on cancer cells compared to the free phytochemical while maintaining very low toxicity in healthy cells. The results suggest a biocompatible and safe nanosystem and a promising anticancer candidate for theranostic applications.