Fluorescent Polystyrene–Fe3O4 Composite Nanospheres for In Vivo Imaging and Hyperthermia

Adv. Mater. 2009, 21, 1–4 2009 WILEY-VCH Verlag Gmb Although many research programs focus on surfacefunctionalized quantum dots (QDs) as clinical tools to improve medical diagnosis, the primary objective of these investigations has been imaging and only a limited number of studies have explored other functionalities, including therapeutic treatment using hyperthermia. The main purpose of this work is to present a new strategy in biomedical nanotechnology that allows simultaneous in vivo imaging and local therapy via hyperthermia. This novel concept is based on a unique nanostructure consisting of polystyrene nanospheres (PS NSs, ca. 100 nm in diameter) fabricated with a narrow size distribution that are modified by polyethylene oxide and that contain Fe3O4 nanoparticles (5–10 nm) embedded in their matrices. QDs are immobilized on the surfaces of these composite NSs, facilitating fluorescent imaging. The Fe3O4 nanoparticles encapsulated in the NSs respond to an external magnetic field by increasing the temperature of the surrounding environment (i.e., hyperthermia), which can be used therapeutically to treat tumor cells locally. A schematic representation of the nanostructure design used to produce magnetic NSs with surface-immobilized QDs (QD–MNSs) is shown in Figure 1. The polyethylene-oxidemodified PS–Fe3O4 NSs were synthesized by miniemulsion/ emulsion polymerization. Earlier research demonstrated that particle size critically affects the superparamagnetic state of the Fe3O4 nanoparticles and must be controlled for biomedical applications. However, this work was limited to the use of individual Fe3O4 nanoparticles in the range 5–10 nm because of: 1) bioincompatibility in medical diagnosis and treatment; 2) aggregation of small particles that precluded homogenous dispersion in aqueous solutions; and 3) weak magnetic moments leading to insufficient heating and a low driving force required for magnetic manipulation. The synthesis of a nanoscale spherical composite with a high fraction of magnetite in its matrix can effectively maintain considerablemagneticmoments in an applied field for both hyperthermia and magnetic guiding. Immobilization of QDs on the surfaces of such MNSs introduces additional properties that are desirable for localized cancer diagnosis. First, QDs on the NS surfaces exhibit intense emission in the near-IR range of the electromagnetic spectrum, which is ideal for deep-tissue imaging. Second, introduction of multivalent, surface-functionalized QDs