Engineering focused ultrasound for glioblastoma

Focused ultrasound (FUS) is a rapidly advancing noninvasive energy delivery technology with the capacity to precisely modulate the tumor microenvironment (TME) through acoustic waves. Glioblastoma (GBM) is characterized by profound TME immune suppression and treatment resistance and has emerged as a key subject to treatment with FUS therapy.

This review examines the technical evolution of FUS and its expanded applications in GBM, including subtypes of low- and high-intensity FUS and their mechanistic contributions to therapeutic effect.

A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar to identify preclinical and clinical studies utilizing FUS in the context of GBM. Articles were included if they discussed FUS mechanisms (thermal, mechanical), bioeffects (immunomodulation, barrier permeability, cell death), or combinatory approaches (e.g., drug delivery, CAR T cells, sonodynamic therapy).

A literature search yielded 312 studies; 95 met inclusion criteria (67 preclinical, 14 clinical trials, 14 reviews) with defined FUS parameters and biological endpoints. FUS enables spatiotemporal control of thermal and mechanical effects in GBM. Modulation of duty cycle, acoustic pressure, and exposure time allows FUS to operate across therapeutic regimes. Preclinical data support using FUS for targeted drug delivery, immune cell repolarization, and synergistic effects with immunotherapies. Clinical trials demonstrate the safety and feasibility of several FUS platforms.

FUS offers a tunable multimodal platform with the potential to overcome core resistance mechanisms in GBM. Recurrent glioblastoma could be effectively treated by integrating FUS as an adjunct therapy alongside emerging immunotherapies and targeted drug delivery systems.