| 초록 |
Arsenic trioxide (ATO) is emerging as a front line agent for treatment of acute promyelocytic leukemia. However, expansion of clinical use is limited because it is unstable in an aqueous phase and has a severe toxicity. Nonetheless, these drawbacks 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) nanoparticle 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. |
