Hypoxia-degradable zwitterionic phosphorylcholine drug nanogel for enhanced drug delivery to glioblastoma

Abstract

As one of the most malignant tumors, glioblastoma encounters the undesirable chemotherapeutic efficacy owing to the short blood circulation, blood–brain-barrier (BBB) and uncontrollable drug release. Although various drug delivery systems have been developed to overcome the above obstacles, the overly complex design and preparation limit their potential clinical applications. Herein, we report one-step fabrication of a hypoxia-degradable zwitterionic phosphorylcholine nanogels named as HPMPC for enhanced chemotherapy of glioblastoma. The obtained HPMPC nanogels with uniform diameter show favorable biocompatibility, anti-fouling ability in mouse serum and long-circulating property in blood. Furthermore, the HPMPC nanogels could pass through the BBB effectively without any targeting groups or outside stimulus due to the mimicking cell membrane structure of phosphorylcholine polymers, which leads to the long-lasting accumulation of the nanogel in glioblastoma tissue. In addition, the HPMPC nanogels composed of azobenzene-contained crosslinker could be degradable in hypoxic environment, leading to the collapse of the nanogel and fast release of the loaded drug in tumor hypoxic tissue. Overall, the HPMPC drug nanogels exhibit favourable tumor inhibition effect in a glioblastoma model with negligible side effects, which may provide a facile and potential nanoplatform to treat various hypoxic relevant diseases in central nervous system.