Dual Functionalized Janus Nanocomposites for Targeted pH-Responsive Drug Delivery
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Dual Functionalized Janus Nanocomposites for Targeted pH-Responsive Drug Delivery Feng Wang1, Giovanni Pauletti2, Yilong Wang3 and Donglu Shi1* 1 The Materials Science and Engineering Program, University of Cincinnati Cincinnati, OH 45221(USA), 2 James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267 (USA), 3 The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, 200092, China. ABSTRACT A superparamagnetic Janus nanocomposite (SJNC) of polystyrene/Fe3O4@SiO2 was designed and developed with dual surface bearing functional groups for medical diagnosis and treatment. Folic acid (FA) and doxorubicin (DOX) were conjugated stepwise to the surfaces. SJNCs were found to enable simultaneous cell-targeted drug delivery via pH-responsive release mechanism. INTRODUCTION There has been an increasing need of nanotechnology that can address the key clinical issues in drug delivery, cell targeting, hyperthermia, and imaging, preferably in a combined fashion, thus improving both cancer diagnosis and treatment. Extensive study has been carried out on establishing nanocarrier systems with multiple functionalities. One of the critical issues in developing multifunctional carriers is the difficulties involved in conjugating a variety of components on a single nanoparticle that is typically symmetrical. These components are needed for necessary medical diagnosis and treatment. For instance, drug must be loaded for cancer cell killing; tumor specific ligands need to be conjugated for cell targeting; fluorescent materials must be installed for optical imaging, and superparamagnetic nanoparticles can also be used for hyperthermia and separation. Therefore the architecture of multiple components has been a great challenge in the engineering of the nanocarriers. In addition, the nanocarriers must be biocompatible and even biodegradable for clinical applications. Although there have been intense efforts on the development of multifunctional nanocariers, 1 most of the approaches rely on symmetrical nanoparticles for various functionalizties that deal with loading of different drugs,2 biological molecules, such as DNA,3 RNA,4 peptide,5 antibodies,6 and imaging probes using quantum dots.7 In these previous developments, a common characteristic is conjugation of each component via a single surface structure. A nanoparticle is normally structurally a symmetrical spherical, or a tubular geometry with limited surface available for multiple components. Furthermore, multi components conjugated on a single carrier can potentially interact with each other, leading to adverse effects. The design and assembly of a single surface symmetrical carrier is also complicated by difficulties in the chemical and spatial arrangements of the functional components. It is, therefore, critical to develop multi-surface nanostructures for assembly of a variety of components on a clinically viable delivery system that can best utilize the intrinsic properties of nanomaterials. Considering the
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