Biodegradable yolk-shell microspheres for ultrasound/MR dual-modality imaging and controlled drug delivery

A new class of uniform biodegradable yolk-shell Fe₃O₄@PFH@PMAA-DOX microspheres was developed as ultrasound/MR dual-modality imaging contrast agents and drug delivery system. PMAA shells exhibit excellent drug loading capability and efficiency, the DOX-loading capacity is 15.4wt% and the drug loading efficiency is 91%. In vivo ultrasound and MRI experiments indicate that the as-prepared Fe₃O₄@PFH@PMAA-DOX microspheres successfully reach tumor tissues and possess robust dual-modality imaging capability, the r₂ value of MRI is 71.82mM^-1s^-1. In vitro cytotoxicity and in vivo tissues biopsies show that the loaded DOX can be control-released under pH, redox and ultrasound multi-stimuli and kill cancer cells effectively. Furthermore, disulfide-crosslinked PMAA shells and PGA-stabilized Fe₃O₄ cores can be respectively degraded into short hydrophilic polymer chains and iron ions, reducing their cumulative toxicity in organisms. Thus, the multifunctional biodegradable microspheres are safer for normal tissues and more beneficial in actual clinical applications.