Engineered nanomedicine remodels the postoperative cavity microenvironment to suppress glioblastoma recurrence

Glioblastoma (GBM) has a high rate of post-surgical recurrence, which can be attributed to residual tumor cells as well as to the disruption of the tumor microenvironment (TME) caused by surgery. Here, we define the postoperative cavity microenvironment (POCM) as a pathological niche with distinct spatial and temporal boundaries, and present a list of markers that outline this environment, including low pH, high levels of reactive oxygen species (ROS), high levels of glutathione (GSH), overexpression of matrix metalloproteinases, and tumor tissue mechanical instability. Engineered nanomedicine is evolving from simple drug-carrying entities to the design of smart responsive materials that can be actively tuned to modulate the POCM. In this review, we outline the working mechanisms and main features of different classes of smart responsive materials, which not only release therapeutic agents but also provide spatiotemporal control over drug delivery, enhance penetration into residual tumor tissue, and trigger immune activation at the right time and place. We discuss how local delivery of nanogel-based platforms in combination with systemic immunotherapy and fine-tuning by means of 3D bioprinting and/or microfluidic chip-based platforms can provide effective tools for reducing post-operative GBM recurrence rates.