Penetrative and Sustained Drug Delivery Using Injectable Hydrogel Nanocomposites for Postsurgical Brain Tumor Treatment

Abstract

Postsurgical treatment of glioblastoma multiforme (GBM) by systemic chemotherapy and radiotherapy is often inefficient. Tumor cells infiltrating deeply into the brain parenchyma are significant obstacles to the eradication of GBM. Here, we present a potential solution to this challenge by introducing an injectable thermoresponsive hydrogel nanocomposite. As a liquid solution that contains drug-loaded micelles and water-dispersible ferrimagnetic iron oxide nanocubes (wFIONs), the hydrogel nanocomposite is injected into the resected tumor site after surgery. It promptly gelates at body temperature to serve as a soft, deep intracortical drug reservoir. The drug-loaded micelles target residual GBM cells and deliver drugs with a minimum premature release. Alternating magnetic fields accelerate diffusion through heat generation from wFIONs, enabling penetrative drug delivery. Significantly suppressed tumor growth and improved survival rates are demonstrated in an orthotopic mouse GBM model. Our system proves the potential of the hydrogel nanocomposite platform for postsurgical GBM treatment.