Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

Abstract

In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.