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Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma.
Li, Yong; Wang, Yixuan; Gao, Lun; Tan, Yinqiu; Cai, Jiayang; Ye, Zhang; Chen, Ann T; Xu, Yang; Zhao, Linyao; Tong, Shiao; Sun, Qian; Liu, Baohui; Zhang, Shenqi; Tian, Daofeng; Deng, Gang; Zhou, Jiangbing; Chen, Qianxue.
Afiliação
  • Li Y; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Wang Y; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Gao L; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Tan Y; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Cai J; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Ye Z; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Chen AT; Department of Neurosurgery, Yale University, New Haven, CT, 06510, USA.
  • Xu Y; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Zhao L; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Tong S; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Sun Q; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Liu B; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Zhang S; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Tian D; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
  • Deng G; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China. gang.deng@whu.edu.cn.
  • Zhou J; Department of Neurosurgery, Yale University, New Haven, CT, 06510, USA. gang.deng@whu.edu.cn.
  • Chen Q; Department of Neurosurgery, Yale University, New Haven, CT, 06510, USA. jiangbing.zhou@yale.edu.
J Nanobiotechnology ; 20(1): 39, 2022 Jan 21.
Article em En | MEDLINE | ID: mdl-35062946
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Nanopartículas / Triterpenos Pentacíclicos / Antineoplásicos Fitogênicos Limite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Nanopartículas / Triterpenos Pentacíclicos / Antineoplásicos Fitogênicos Limite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Ano de publicação: 2022 Tipo de documento: Article