An α-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy

초록

Nanoassembly (NA) based on a D-alpha-tocopherol succinate (alpha TS) conjugated lysozyme (Lys) (Lys-alpha TS) was fabricated for tumor-selective delivery of curcumin (CUR) for breast cancer therapy. Lys and alpha TS were used as a biocompatible enzyme and a hydrophobic residue, respectively, for the preparation of nanocarriers in this study. Compared with CUR-loaded cross-linked Lys (c-Lys/CUR) NA, Lys-alpha TS/CUR NA exhibited a smaller hydrodynamic size (213nm mean diameter), a narrower size distribution, and a more spherical shape. Sustained drug release was observed from the Lys-alpha TS/CUR NA for five days at a normal physiological pH (pH 7.4). The developed Lys-alpha TS/CUR NA showed enhanced cellular accumulation, antiproliferative effects, and apoptotic efficacies in MDA-MB-231 human breast adenocarcinoma cells. According to the results of optical imaging test in the MDA-MB-231 tumor-bearing mouse models, the Lys-alpha TS/CUR NA-injected group exhibited a more tumor-selective accumulation pattern, rather than being distributed in the normal tissues and organs. The observed tumor targetability of Lys-alpha TS/CUR was further studied, which revealed improved in vivo anticancer activities (better inhibition of tumor growth and induction of apoptosis in the tumor tissue) after an intravenous administration in the MDA-MB-231 tumor-bearing mouse models. All these results indicate that the newly developed enzyme-based nanocarrier, the Lys-alpha TS NA, can be a promising candidate for the therapy of breast cancers.

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