A Dual pH/Magnetic Responsive Nanocarrier Based on PEGylated Fe₃O₄ Nanoparticles for Doxorubicin Delivery

Cancer chemotherapy has limitations such as nonselective distribution of drugs, detrimental side effects on normal tissues; here we reported a smart pH and magnetic sensitive drug delivery system (DDS) based on PEGylated Fe₃O₄ superparamagnetic nanoparticles. The citric-coated Fe₃O₄ (CIO) nanoparticles were firstly synthesized and further functionalized by biocompatible poly(ethylene glycol) bis(carboxymethyl ether) (COOH-PEG-COOH), thus PEGylated CIO (GCIO) nanoparticles were obtained. Doxorubicin (DOX) was conjugated as a model drug to the nanoparticles via hydrazone bond. The roughly sphere GCIO nanoparticles were comparatively strong magnetism with high drug loading capability (~89%) in relatively uniform size. Drug release study revealed that the GCIO-DOX performed pH-responsive drug-release properties. MTT assay demonstrated that GCIO nanoparticles possessed low cytotoxicity and good physiological stability. Further, cell viability results indicated that the GCIO-DOX showed effective cytotoxicity only a bit lower than free DOX. All obtained data indicated that the combined pH-responsive and magnetic multifunction drug delivery system can has excellent potential applications in cancer therapy.