pH-Responsive Charge-Conversional and Hemolytic Activities of Magnetic Nanocomposite Particles for Cell-Targeted Hyperthermia

[Image: see text] Magnetic nanocomposite particle (MNP)-induced hyperthermia therapy has been restricted by inefficient cellular targeting. pH-responsive charge-conversional MNPs can enhance selective cellular uptake in acidic cells like tumors by sensing extracellular acidity based on their charge alteration. We have synthesized new, pH-induced charge-conversional, superparamagnetic, and single-cored Fe(3)O(4) nanocomposite particles coated by N-itaconylated chitosan (NICS) cross-linked with ethylene glycol diglycidyl ether (EGDE) (Fe(3)O(4)-NICS-EGDE) using a simple, one-step chemical coprecipitation–coating process. The surface of the Fe(3)O(4)-NICS-EGDE nanocomposite particles was modified with ethanolamine (EA) via aza-Michael addition to enhance their buffering capacity, aqueous stability, and pH sensitivity. The designed Fe(3)O(4)-NICS-EGDE-EA nanocomposite particles showed pH-dependent charge-conversional properties, colloidal stability, and excellent hemocompatibility in physiological media. By contrast, the charge-conversional properties enabled microwave-induced hemolysis only under weakly acidic conditions. Therefore, the composite particles are highly feasible for magnetically induced and targeted cellular thermotherapeutic applications.