초록 |
Arsenic trioxide(ATO) is an emerging anticancer drug for treatment of various solid tumors. However, its therapeutic use is limited because of the instability in an aqueous phase and dose-limiting toxicity. Nonetheless, these disadvantages could be resolved by employing nanocarrier systems incorporated with a transitional metal-arsenite complex. Herein, we developed a self-assembled poly(ethylene glycol)-b-poly(L-dihydroxyphenylalanine) (PEG-P(L-DOPA)) nanoparticle that formed Ni(II) arsenite complexes on the P(L-DOPA)core domain. The Ni(II) arsenite complexes would effectively improve the structural stability of PEG-P(L-DOPA) nanoparticles in an aqueous phase. The release of ATO would be inhibited at physiological pH(7.4), whereas, at an endosomal pH(5.0), the release of ATO was triggered by ionization of the Ni(II) arsenite complexes. This novel polymer nanoparticle containing Ni(II)-chelating P(L-DOPA)cores would enable the stable loading and effective intracellular delivery of ATO. |