Dopamine-Conjugated Bovine Serum Albumin Nanoparticles Containing pH-Responsive Catechol-V(III) Coordination for In Vitro and In Vivo Drug Delivery

Abstract

V(III) instead of commonly used Fe(III) provided a richtris-catechol-metalcoordination at pH 7.4, which is important for slow drug release atphysiological pH. Bovine serum albumin (BSA) functionalized with catechol-containingdopamine (D) and cross-linked using tris-catechol-V(III) coordinationyielded pH-responsive compact D-BSA NPs (253 nm). However, conversionto bis- and/or mono-catechol-V(III) complexes in an acidic mediumresulted in degradation of NPs and rapid release of doxorubicin (DOX).It was shown that D-BSA NPs entered cancerous MCF-7 cells (66%) moreefficiently than non-cancerous HEK293T (33%) in 3 h. Also, DOX-loadedNPs reduced cell viability of MCF-7 by 75% and induced apoptosis ina majority of cells after 24 h. Biodegradability and lack of hemolyticactivity were shown in vitro, whereas a lack of toxicity was shownin histological sections of zebrafish. Furthermore, 30% of circulatingtumor cells in vasculature in 24 h were killed by DOX-loaded NPs shownwith the zebrafish CTC xenograft model.