Poly(N-isopropylacrylamide)-coated thermo-responsive nanoparticles for controlled delivery of sulfonated Zn-phthalocyanine in Chinese hamster ovary cells in vitro and zebra fish in vivo

摘要

Poly(N-isopropylacrylamide) (PNIPAM)-coated Fe_3O_4@SiO_2@CdTe multifunctional nanoparticles with photoluminescent (PL), thermoseositive and magnetic properties, were investigated as carriers to deliver water-soluble, fluorescent sulfonated Zn-phthalocyanine (ZnPcS), a photosensitizing drug for photodynamic therapy of cancer, in Chinese hamster ovary (CHO) cells in vitro and zebra fish in vivo. PNIPAM is a well-known thermo-responsive polymer with a volume phase transition temperature. This property allows it to be swollen in water at temperatures lower than 32-34 deg C to take up ZnPcS and shrunken to expel the drug at higher temperatures. Since the PL band of CdTe quantum dots (QDs) as indicators for the nanoparticles is at 585 nm and the emission band of ZnPcS is at 680 nm, it is possible to study the temperature-dependent release of ZnPcS from the nanoparticles by fluorescence measurements. ZnPcS was embedded in the PNIPAM of the nanoparticles at 25 deg C in phosphate buffered saline (PBS) solution and released at 37 deg C, measured with a spectrophotometer. When CHO cells had been incubated with the ZnPcS-loaded nanoparticles at 27 deg C, a similar intracellular localization pattern of CdTe QDs and ZnPcS was seen by multichannel measurements in confocal laser scanning microscopy (CLSM), but a diffuse pattern of only ZnPcS fluorescence was detected in the cytoplasm of the cells at 37 deg C, indicating a release of ZnPcS from the nanoparticles. Similar results were also found in the intestinal tract of zebra fish in vivo after intake of the nanoparticles. Since the nanoparticles contain magnetic (Fe_3O_4) material, the nanoparticles could also be manipulated to change their location in the intestinal tract of the zebra fish with an external magnetic field gradient of 300 G mm~(-1). The results presented suggest that such multifunctional nanoparticles may have combined potential for temperature-dependent drug delivery, QD photodetection and magnetic manipulation in diagnosis and therapy of diseases.