Accurately Controlled Delivery of Temozolomide by Biocompatible UiO-66-NH2 Through Ultrasound to Enhance the Antitumor Efficacy and Attenuate the Toxicity for Treatment of Malignant Glioma

Abstract

Background: Glioma is the most common and malignant primary brain tumour in adults and has a dismal prognosis. Temozolomide (TMZ) is the only clinical first-line chemotherapy drug for malignant glioma up to present. Due to poor aqueous solubility and toxic effects, TMZ is still inefficient and limited for clinical glioma treatment. Methods: UiO-66-NH 2 nanoparticle is a zirconium-based framework, constructed by Zr and 2-amino-1,4-benzenedicarboxylic acid (BDC-NH 2 ) with octahedral microporous structure, which can be decomposed by the body into an ionic form to discharge. We prepared the nanoscale metal-organic framework (MOF) of UiO-66-NH 2 to load TMZ for therapy of malignant glioma, TMZ is released from UiO-66-NH 2 through a porous structure. The ultrasound accelerates its porous percolation and promotes the rapid dissolution of TMZ through low-frequency oscillations and cavitation effect. The biological safety and antitumor efficacy were evaluated both in vitro and in vivo. Results:The prepared TMZ@MOF exhibited excellent biocompatibility and biosafety due to minimal drug leakage without ultrasound intervention. We further used the flank model of glioblastoma to verify the in vivo therapeutic effect.

Metal–Organic Frameworks‐Based Nanoplatforms for the Theranostic Applications of Neurological Diseases

“…[ 159 ] Therefore, UiO‐66‐NH 2 nanoparticle was constructed for accurate and rapid delivery of TMZ under the intervention of US through US‐mediated cavitation effect and low‐frequency oscillation. [ 149 ] The synthesized TMZ@UiO‐66‐NH 2 nanoparticles showed excellent biosafety as the result of minimal drug leakage without US irradiation in vitro. In the model of xenograft neuroglioma, TMZ@UiO‐66‐NH 2 could be well enriched in the tumor tissue under US, leading to more efficient suppression of tumor growth than both TMZ@UiO‐66‐NH 2 nanoparticles and TMZ.…”

Metal–Organic Frameworks for Nerve Repair and Neural Stem Cell Therapy

“…Low-intensity focused US can be applied to induce acoustic cavitation, generating oscillating bubbles in the proximity of Reproduced with permission. [35] Copyright 2021, International Journal of Nanomedicine. b) Synthesis of the UIO-66-Au NPs for improved piezoelectric SDT and nanoenzyme catalytic therapy.…”

“…MOFs-based ultrasound therapy for nerve repair. a) Schematic diagram of ultrasonic controlled TMZ@UiO-66-NH 2 drug delivery system.Reproduced with permission [35]. Copyright 2021, International Journal of Nanomedicine.…”

Metal-based nano-delivery platform for treating bone disease and regeneration

“…Zr MOFs can be used to deliver different drugs or active ingredients when treating different bone diseases. For example, small molecule drugs can be delivered using UiO-66-NH2 NPs such as DOX, cisplatin, temozolomide, and curcumin ( Ma et al, 2020 ; Fytory et al, 2021 ; Wan et al, 2021 ; Hu et al, 2022 ). In addition, a few single metal atoms (Pt, Au, Cu, Ru) can be delivered using PCN-222 ( Yu et al, 2022 ).…”