PEGylated hyperbranched polyphosphoester based nanocarriers for redox-responsive delivery of doxorubicin

Redox-responsive polymers exhibit great potential as drug delivery systems. Herein, a redox-responsive PEGylated hyperbranched polyphosphoester (PPE) was synthesized through (A(2) + B-3) type polycondensation. The obtained hyperbranched PPE can self-assemble into nanoparticles in water. The biocompatibility of the nanoparticles was evaluated. The hydrophobic chemotherapy drug doxorubicin (DOX) can be efficiently encapsulated into the obtained nanoparticles. Such DOX-loaded nanoparticles exhibited excellent stability due to the PEGylation, and showed redox-responsive drug release behavior. In addition, flow cytometric analyses demonstrated that the redox-responsive nanoparticles could be efficiently internalized into the human breast cancer cell line MDA-MB-231, and intracellular glutathione enhanced the intracellular drug release from the redox-responsive hyperbranched PPE based nanoparticles. Therefore, such nanoparticles resulted in the enhanced inhibition of tumor cell growth, suggesting the potential of redox-responsive PEGylated hyperbranched PPE in anticancer drug delivery.