We describe the development of multifunctional polymeric micelles with cancer-targeting capability via rvâ3 integrins, controlled drug delivery, and efficient magnetic resonance imaging (MRI) contrast characteristics. Doxorubicin and a cluster of superparamagnetic iron oxide (SPIO) nanoparticles were loaded successfully inside the micelle core. The presence of cRGD on the micelle surface resulted in the cancer-targeted delivery to rvâ3-expressing tumor cells. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and rvâ3-specific cytotoxic response of these multifunctional polymeric micelles.

Diblock copolymers of poly(q-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 Ag ml 1, while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 jC demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.

Furosemide microcrystals were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 5-mm drug microcrystals through layer-bylayer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin /PSS bilayers with corresponding capsule wall thicknesses ranging from 45 to 115 nm. The release of furosemide from the coated microparticles was measured in aqueous solutions of pH 1.4 and 7.4. At both pH values, the release rate of furosemide from the encapsulated particles was reduced by 50–300 times (for capsules coated with two to six bilayers) compared to uncoated furosemide. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug microcrystals.

Platelets were coated with 78-nm silica nanoparticles, 45-nm fluorescent nanospheres, or bovine immunoglobulin G (IgG) through layer-by-layer assembly by alternate adsorption with oppositely charged linear polyions. Sequential deposition on platelet surfaces of cationic poly(dimethyldiallylammonium chloride) and anionic poly(styrene sulfonate) was followed by adsorption of nanoparticles or immunoglobulins. Nanoorganized shells of platelets were demonstrated by transmission electron microscopy and fluorescence microscope images. Bovine IgG was assembled on platelets, as verified with anti-bovine IgG-FITC labeling. Localized targeting of anti-IgG shelled platelets was also demonstrated. An ability to coat blood cells with nano-organized shells can have applications in cardiovascular research and targeted drug delivery.

Furosemide microcrystals were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 5-mm drug microcrystals through layer-bylayer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin /PSS bilayers with corresponding capsule wall thicknesses ranging from 45 to 115 nm. The release of furosemide from the coated microparticles was measured in aqueous solutions of pH 1.4 and 7.4. At both pH values, the release rate of furosemide from the encapsulated particles was reduced by 50-300 times (for capsules coated with two to six bilayers) compared to uncoated furosemide. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug microcrystals.