Chemotherapy is often hindered by issues associated with deficient drug selectivity and ineluctable toxic effects. The emerging realm of mechanochemistry has demonstrated significant promise in precise drug activation by using ultrasound-induced mechanical forces to regulate the chemical properties of compounds at the molecular level. Recently, we proved that the successful introduction of nanostructures to mechanochemistry could improve drug loading capacity and enhance their mechanical responsiveness. To further expand the application of the ultrasound-response drug activation strategy in nanosystems, in this context, we illustrate the preparation of a mechano-nanoswitch for spatiotemporal control of drug activation.

Brain cancer, also known as intracranial cancer, is one of the most invasive and fatal cancers affecting people of all ages. Despite the great advances in medical technology, improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier (BBB). Fortunately, recent endeavors using gold-based nanomaterials (GBNs) have indicated the potential of these materials to cross the BBB. Therefore, GBNs might be an attractive therapeutic strategy against brain cancer. Herein, we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment. Furthermore, the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized, with an emphasis on the mechanism of their effective BBB penetration. Finally, the challenges and future outlook in using GBNs for brain cancer treatment are discussed. We hope that this review will spark researchers’ interest in constructing more powerful nanoplatforms for brain disease treatment.