Glioblastoma (GBM), the most aggressive grade IV malignant tumor in the central nervous system, presents a poor prognosis. Despite extensive insights into its molecular pathology, the conventional Stupp regimen remains largely ineffective due to several factors, including diffuse tumor infiltration, radioresistance, the blood-brain barrier (BBB), and therapy resistance driven by GBM stem cells (GSCs). Research has established that epigenetic modifications play a crucial role in the initiation, progression, invasion, and treatment resistance of GBM. However, existing epigenetic modulators frequently encounter pharmacokinetic limitations, which significantly compromise their efficacy. As a result, there is an urgent need for novel technologies to enhance the therapeutic impact of epigenetic modulators in GBM. This article reviews and discusses current GBM treatments, with a particular emphasis on the rapidly evolving strategy of nanomedicine. By encapsulating epigenetic modulators in precisely engineered nanocarriers, this approach not only improves drug solubility, stability, and circulation time, but also enhances tumor accumulation through passive or active targeting strategies, while allowing for controlled and intelligent drug release. Importantly, specially designed nanocarrier systems can effectively cross the BBB and overcome drug resistance, paving the way for new drug delivery methods in the management of GBM.

Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes. In this regard, we propose “mineral-in-shell nanoarchitectonics”, inspired by the nanostructure of matrix vesicles, which can influence multiple mineralization pathways. Our nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid (TA) and silk fibroin (SF) nanoshell. The bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures, followed by large-scale intradentinal mineralization both in vitro and in vivo, which provides persistent protection against external stimuli. Theoretical simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell, which exhibits a strong affinity for the dentin structure, stabilizing amorphous precursors and thereby facilitating concomitant mineral formation. Overall, this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.

The invasion of etched dentinal tubules (DTs) by external substances induces dentin hypersensitivity (DH). The deep and compact occlusion of DTs is highly desirable for treating DH but still challenging due to the limited penetrability and mineralization capacities of most current desensitizers. Matrix vesicles (MVs) participate in the regulation of ectopic mineralization. Herein, ectopic MV analogs are prepared by employing natural cell membranes to endow mineral precursors with natural biointerfaces and integrated biofunctions for stimulating dentin remineralization. The analogs quickly access DTs (> 20 μm) in only 5 min and further penetrate deep into the interior of DTs (an extraordinary ~ 200 μm) in 7 days. Both in vitro and in vivo studies confirm that the DTs are efficiently sealed by the newly formed minerals (> 50 μm) with excellent resistance to wear and acid erosion, which is significantly deeper than most reported values. After repair, the microhardness of the damaged dentin can be recovered to those of healthy dentin. For the first time, cell membrane coating nanotechnology is used as a facile and efficient therapy for in-depth remineralization of DTs in treating DH with thorough and long-term effects, which provides insights into their potential for hard tissue repair.