Microneedle patch integrated with hydroxyapatite nanoparticles and abemaciclib for treatment of meningioma.

Abstract

Surgery remains the primary treatment for meningiomas, with radiotherapy used for high-grade tumors, residual disease, and recurrences. However, many high-risk meningiomas progress despite resection or radiotherapy, and effective pharmacological therapies remain lacking. Here, we explored a local microneedle-mediated delivery strategy using gelatin methacryloyl hydrogels (Gel-MA) to co-deliver hydroxyapatite nanoparticles (n-HA) and the selective CDK4/6 inhibitor abemaciclib in meningioma cell-line models. n-HA and abemaciclib were associated with reduced proliferation, increased apoptosis-related signals, and cell-cycle inhibition in the tested models. Exploratory RNA sequencing suggested that n-HA treatment was associated with transcriptional changes related to cellular stress, calcium homeostasis, apoptosis, endocytosis, and immune-related pathways; these findings should be interpreted as hypothesis-generating rather than definitive mechanistic evidence. In an orthotopic xenograft model, local microneedle delivery of n-HA and abemaciclib suppressed tumor progression and was associated with treatment-related histological changes. Overall, this study provides proof-of-concept evidence that a biodegradable microneedle platform may enable local combination therapy for residual, recurrent, or incompletely resectable meningiomas. STATEMENT OF SIGNIFICANCE: Hydroxyapatite nanoparticles (n-HA), a bone-like material, suppress meningioma cell growth while stimulating anti-tumor immune responses, suggesting a therapeutic role beyond structural biomaterials. We further show that n-HA synergizes with abemaciclib to enhance tumor inhibition and immunity. To deliver this combination precisely to the tumor site, we develop GelMA microneedle patches that enable localized and controlled release, reducing reliance on systemic dosing. In animal models, microneedles loaded with n-HA and abemaciclib produce marked anti-tumor effects. Finally, incorporating β-cyclodextrin improves abemaciclib bioavailability, strengthening local therapy. Together, this work introduces an immunoactive biomaterial-drug microneedle strategy with potential for safer, more effective meningioma treatment.