| Fullerene (C60) has special structure and optical properties, having shownpotential promise in delivery of drugs and photodynamic therapy, while itsbiomedical applications are limited owing to its high hydrophobicity. In this study,iron oxide nanoparticles (IONP) and PEGylation were decorated onto the surface offullerene (C60), obtaining a novel C60-IONP-PEG nanocomposite with strongsuperparamagnetism and high hydrophily. Hematoporphyrin monomethyl ether(HMME), a new photodynamic anti-cancer drug, was conjugated to C60-IONP-PEG,forming a C60-IONP-PEG/HMME multifunctional drug delivery system whichdemonstrated excellent photodynamic therapy (PDT) efficacy, magnetic targetingproperty and magnetic resonance imaging (MRI) ability.In this study, the first step was to synthesize fullerene derivatives as drugcarriers. C60-IONP-COOH was synthesized by bingle cycloaddition reaction,esterhydrolysis reaction and hydro thermal reaction. PEGylation was performed via acondensation of carboxyl of C60-IONP and NH2group of PEG(2000)-NH2, formingmagneticvector system C60-IONP-PEG. C60-IONP-PEG was characterized byfourier transmission infrared spectroscopy (FT-IR), transmission electronmicroscopy (TEM) and dynamic laser scattering (DLS). A vibrating samplemagnetometer (VSM) was used for characterizing the magnetic property ofC60-IONP-PEG. The relative amount of PEG linked to C60-IONP was tested using athermal gravimetric analysis (TGA). T2-weighted MR scheme of C60-IONP-PEGwas conducted on a3-T clinical MRI scanner. The results showed thatC60-IONP-PEG was successfully synthetized, which demonstrated highhydrophily,strong superparamagnetism andMRIability.C60-IONP-PEG showedappropriate size and zeta potential, which could be used as an excellent magnetictargeted drug delivery carrier.In this study HMME was chosenas a model drug. The prescription craft of thetumor targeted drug delivery system C60-IONP-PEG/HMME was determined through single factor experiment concerning reactant ratio, ultrasonic power andultrasonic time on the impact of loading capacity. DLS, TEM and UV-vis wererespectively used for characterizing this system.The results showed thatHMME wasloaded onto C60-IONP-PEG with high loading efficacy (~125.3%). This systemremained stable and had uniform particle size distribution. Moreover, HMME releasefrom C60-IONP-PEG was sustained over120h.The photodynamic therapy was investigated with mice melanoma (B16-F10)cells in vitro. Cell experiments indicated that C60-IONP-PEG exhibited low toxicity,but it had high ROS productions with532nm laser exposure. Both C60and HMMEcould efficiently generate ROS with532nm laser exposure, thereforegreatlyimproved the photodynamic efficacy andremarkably enhanced cancer cells killingeffect were observed for B16-F10cells treated by C60-IONP-PEG/HMME. Laserpower density-dependent and concentration-dependent cytotoxicity of all groupswere shown. C60-IONP-PEG/HMME showed a strong inhibition effect on cancercells near the magnetic field. The T2weighted signal intensity of B16-F10cellsdisplayed a significant decrease with the concentration dependent darkening effect inMRI images.C57mice melanoma tumor models were generated by subcutaneous injection ofB16-F10cells.The study respectively investigated the tumor inhibition effect ofC60-IONP-PEG/HMME, C60-IONP-PEG and HMME with or without light. Theresults showed that C60-IONP-PEG/HMMEwere clustered together near the tumorsite, andafter532nm laser exposure it had a stronger effect for the treatment oftumorin comparison to those of C60-IONP-PEGor HMME. In vivo MRIexperiments suggest that the T2weighted signal intensity of tumor, liver, spleen andkidney were remarkably reduced. C60-IONP-PEG could act as a suitable negative T2contrast agent in MRI applications.In summary, C60-IONP-PEG/HMME showed magnetic targetingproperty,excellent PDT efficacy and MRI ability, indicating that there is a greatpotential of C60-IONP-PEG/HMME for cancer theranostic applications. |
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