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ACS Central Science

ACS Central Science

IF: 12.7
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Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma

Published:21 January 2022 DOI: 10.1186/s12951-022-01238-7 PMID: 35062946
Yong Li,?Yixuan Wang,?Lun Gao,?Yinqiu Tan,?Jiayang Cai,?Zhang Ye,?Ann T Chen,?Yang Xu,?Linyao Zhao,?Shiao Tong,?Qian Sun,?Baohui Liu,?Shenqi Zhang,?Daofeng Tian,?Gang Deng,?Jiangbing Zhou,?Qianxue Chen

Abstract

Background: Glioblastoma (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). Due to the existence of blood-brain barrier (BBB), most therapeutics cannot efficiently reach tumors in the brain, and as a result, they are unable to be used for effective GBM treatment. Accumulating evidence shows that delivery of therapeutics in form of nanoparticles (NPs) may allow crossing the BBB for effective GBM treatment.

Methods: Betulinic acid NPs (BA NPs) were synthesized by the standard emulsion approach and characterized by electron microscopy and dynamic light scattering analysis. The resulting NPs were characterized for their anti-tumor effects by cell viability assay, EdU-DNA synthesis assay, cell cycle assay, mitochondrial membrane potential, and PI-FITC apoptosis assay. Further mechanistic studies were carried out through Western Blot and immunostaining analyses. Finally, we evaluated BA NPs in vivo for their pharmacokinetics and antitumor effects in intracranial xenograft GBM mouse models.

Results: BA NPs were successfully prepared and formed into rod shape. BA NPs could significantly suppress glioma cell proliferation, induce apoptosis, and arrest the cell cycle in the G0/G1 phase in vitro. Furthermore, BA NPs downregulated the Akt/NFκB-p65 signaling pathway in a concentration dependent manner. We found that the observed anti-tumor effect of BA NPs was dependent on the function of CB1/CB2 receptors. Moreover, in the intracranial GBM xenograft mouse models, BA NPs could effectively cross the BBB and greatly prolong the survival time of the mice.

Conclusions: We successfully synthesized BA NPs, which could cross the BBB and demonstrated a strong anti-tumor effect. Therefore, BA NPs may potentially be used for effective treatment of GBM.

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