Studies On Poly(Ether-anhydride)Micelles With Different Morphologies As Antitumor Drug Carriers

For cancer therapy, optimization of carrier features is necessary to effectively deliver the targeting agents to tumor sites. Biodegradable poly(ether-anhydrides) micelles with spherical (S), rod-like (R) and filamentous (F) shapes are fabricated.Their size and morphology are characterized by Zetasizer, Atomic force microscope (AFM) and Transmission electron microscope (TEM).The doxorubicin hydrochloride (DOX) was used as the drug model, three DOX-loaded micelles with different morphologies, spherical DOX-loaded micelle(DOX-S), rod-like DOX-loaded micelle(DOX-R) and filamentous DOX-loaded micelle(DOX-F), were prepared. The encapsulation of DOX into the micelles does not impact their shape. The effect of micellar shape on the drug loading capacity and encapsulation efficiency, as well as in vitro drug release, was investigated.The cytotoxicity, effect of antitumor and cellular uptakes were evaluated using Alarma blue assay, fluorescence microscopy, confocal laser scanning microscopy and flow cytometry on co-cultures of human hepatoblastoma cell line (HepG2), lung epithelial cancer cell line (A549), and human buccal epidermoid carcinoma cells (KB) and fibroblast normal cells mixed with the different shapes of DOX-loaded micelles. The results showed that the DOX-S were more readily taken up by all types of cells studied.Mouse breast cancer cells(4T1) were used on the Balb/c to evaluate the impact of micellar shape on in vivo antitumor function from changes of tumor volume, body weight loss, and survival rate of4T1-bearing mice and the immunostaining of tumor sections for analysis of tumor cell proliferation. The results reveal that the DOX-F possess the highest safety to body and the best therapeutic effects to artificial solid tumors.In a word, the filamentous shape is a suitable morphology for design and engineering of drug vehicles for cancer therapy.