Vegetation transpiration contributions to precipitation recycling in a semi-arid grassland: an isotope-constrained source partitioning framework.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, classified as a grade IV astrocytoma by the World Health Organization (WHO) []. Originating from glial cells, which provide support to neurons, GBM is characterized by a highly infiltrative nature, rapid proliferation, and significant resistance to conventional therapies []. The precise etiology of this disease remains largely unknown, but is believed to be due to a complex interplay of genetic, epigenetic, and environmental factors []. The poor prognosis associated with GBM, with a median survival of approximately 15–20 months despite aggressive treatment, underscores the urgent need for innovative and more effective therapeutic strategies [,]. Patients with GBM often present with a variety of neurological symptoms, which are highly dependent on the tumor’s size and location in the brain. The most common manifestations include persistent headaches, nausea and vomiting, seizures, cognitive deficits (e.g., memory problems, language difficulties), personality changes, and focal neurological deficits such as muscle weakness []. The insidious onset and progressive worsening of these symptoms often lead to significant patient morbidity and severe impairment in quality of life. Current treatment for newly diagnosed GBM typically involves maximal surgical resection followed by concurrent radiotherapy and chemotherapy with temozolomide (TMZ), followed by adjuvant TMZ []. Despite these intensive multimodal treatments, the intrinsic biological aggressiveness of GBM, combined with challenges such as the blood–brain barrier (BBB), a formidable physiological barrier that limits the passage of most therapeutic agents into the brain, and intrinsic or acquired drug resistance, significantly limits treatment efficacy and contributes to high relapse rates []. The ineffectiveness of current therapeutic strategies in substantially improving patient outcomes and life expectancy has prompted research to focus on identifying innovative therapeutic molecules and delivery methods with greater efficacy and reduced systemic side effects. In this context, nanoparticle (NP) systems represent a highly promising strategy to overcome the limitations of conventional GBM therapies. Nanoparticles offer several advantages, including their nanoscale size, which facilitates drug delivery across biological barriers, and the possibility of surface functionalization with specific ligands to enable targeted delivery []. Crucially, nanoparticles (NPs) can be engineered to cross the blood–brain barrier (BBB), a formidable physiological barrier that limits the passage of most therapeutic agents into the brain, and to selectively accumulate in tumor tissue via enhanced permeability and retention (EPR) or active targeting mechanisms [,]. This targeted delivery can lead to controlled and sustained release of therapeutic agents directly to the tumor site, thus maximizing their therapeutic index and minimizing off-target toxicity.