| Abstract: | A novel, inexpensive biofunctionalization approach is adopted to develop a multimodal and theranostic nanoagent, which combines cancer‐targeted magnetic resonance/optical imaging and pH‐sensitive drug release into one system. This multifunctional nanosystem, based on an ultrasmall superparamagnetic iron oxide (USPIO) nanocore, is modified with a hydrophilic, biocompatible, and biodegradable coating of N‐phosphonomethyl iminodiacetic acid (PMIDA). Using appropriate spacers, functional molecules, such as rhodamine B isothiocyanate, folic acid, and methotrexate, are coupled to the amine‐derivatized USPIO–PMIDA support with the aim of endowing simultaneous targeting, imaging, and intracellular drug‐delivering capability. For the first time, phosphonic acid chemistry is successfully exploited to develop a stealth, multifunctional nanoprobe that can selectively target, detect, and kill cancer cells overexpressing the folate receptor, while allowing real‐time monitoring of tumor response to drug treatment through dual‐modal fluorescence and magnetic resonance imaging. |
