J.S. Huang, F.Y. Cheng, C.H. Tsai, D.B. Shieh
National Cheng Kung University,
Keywords: superparamagnetic iron oxide nanoparticles, alginate, carbodiimide reaction, drug delivery system, oral cancer
Summary:The development of multifunctional nanocomplexs for drug delivery in oral cancer therapy Oral cancer has been denoted as the sixth most common cancer in the world. Chemotherapy is one of the major therapies for advanced oral cancer cases, besides surgery and radiotherapy. Advances in drug delivery system draw a hope for cancer treatment and a niche for pharmacotherapy industry. A novel drug delivery system made of superparamagnetic iron oxide nanoparticles (SPIONs) covalently linked with alginate was developed for oral cancer therapy. Alginate-conjugated SPION (SPION-alginate) is prepared by mixing magnetite (Fe3O4) nanoparticles functionalized with the-NH3+ group and alginate, followed by carbodiimide reaction. The FT-IR spectra of SPION-alginate reveals that alginates conjugate to Fe3O4 nanoparticles successfully. Doxorubicin (DOX),an anticancer drug, is encapsulated into the drug delivery system by suspending DOX mixed in SPION-alginate solution followed by dropping the mixture into 10 mM CaCl2 aqueous solution(DOX-loaded SPION@Ca-alginate). The initial release phase occurred with 24 hr, and reached the saturation within 48 hr. The release profile indicates that the cumulative DOX release percentage is highest at pH 5.5(44.88±1.76% at 7th day). The cumulative release percentage of DOX depended on the environment in which DOX-loaded Fe3O4@Ca-alginatenanoparticles were immersed. The cumulative release percentage in four different buffers increased in following order: deionized water＜PBS＜PBS with pH value of 5.5＜cytoplasm mimicking buffer. The release profiles of DOX-loaded Fe3O4@Ca-alginatenanoparticles were similar in regardless of the concentration of CaCl2solution that entrapped doxorubicin into alginate matrices. The in vitro cytotoxicity of DOX-loaded Fe3O4@Ca-alginate was evaluated by MTT assay. The cytotoxic activity would be enhanced by lowering Ca2+-crosslinking density. When the Fe3O4@Ca-alginate nanoparticles prepared by 2.5 mM CaCl2, the cell viability decreased to 55% with 1μM of DOX exposure, which was almost identical to that of free DOX. These results suggested Fe3O4@Ca-alginatenanoparticles released drugs in a spatial-controlled manner with higher release percentage in intracellular compartments. Nanocomplexes made of the NH3+ exposed Fe3O4 nanoparticles and alginates can serve as a drug delivery system. The iron oxide core possesses superparamagnetism and excellent biocompatibility, which makes them appreciate for clinical diagnosis and therapy. The alginate moiety accommodates large amount of drugs, and shows efficient intracellular release. The in vitro cytotoxicity data indicates that DOX-loaded Fe3O4@Ca-alginatenanoparticles exhibit a good therapeutic efficiency. These data suggest Fe3O4@Ca-alginatemay be a candidate for good drug delivery systems in cancer therapy.