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-NH2 nanoparticle is a zirconium-based framework, constructed by Zr and 2-amino-1,4-benzenedicarboxylic acid (BDC-NH2) 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-NH2 to load TMZ for therapy of malignant glioma, TMZ is released from UiO-66-NH2 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. TMZ@UiO-66-NH2 nanocomposites could be well delivered to the tumour tissue, which led to local enrichment of the TMZ concentration. Furthermore, TMZ@UiO-66-NH2 nanocomposites under ultrasound demonstrated much more efficient inhibition for tumor growth than TMZ@UiO-66-NH2 nanocomposites and TMZ alone. Meanwhile, the bone marrow suppression side effects of TMZ were significantly reduced by TMZ@UiO-66-NH2 nanocomposites.

CONCLUSION:

In this work, TMZ@UiO-66-NH2 nanocomposites with ultrasound mediation could effectively improve the killing effect of malignant glioma and decrease TMZ-induced toxicity in normal tissues, demonstrating great potential for the delivery of TMZ in the clinical treatment of malignant gliomas.

• Authors: Zhiping Wan, Chunlin Li, Jinmao Gu, Jun Qian, Junle Zhu, Jiaqi Wang, Yinwen Li, Jiahao Jiang, Huairui Chen, Chun Luo
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 16 Pg. 6905-6922 ( 2021) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 34675514 (Publication Type: Journal Article)
• Copyright: © 2021 Wan et al.

Chemical References

• Antineoplastic Agents, Alkylating
• Temozolomide

Topics

• Antineoplastic Agents, Alkylating
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Glioblastoma (drug therapy)
• Glioma (drug therapy)
• Humans
• Temozolomide (therapeutic use)
• Xenograft Model Antitumor Assays