Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma.
Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma.
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β酸自组装的纳米颗粒，可有效治疗胶质母细胞瘤。
DOI：
10.1186/s12951-022-01238-7
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发表时间：
2022-01-21
影响因子：
10.2
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Li Y;Wang Y;Gao L;Tan Y;Cai J;Ye Z;Chen AT;Xu Y;Zhao L;Tong S;Sun Q;Liu B;Zhang S;Tian D;Deng G;Zhou J;Chen Q
胶质母细胞瘤（GBM）是中枢神经系统（CNS）最常见和最致命的原发性肿瘤。由于血脑屏障（BBB）的存在，大多数治疗剂不能有效地到达脑中的肿瘤，因此，它们不能用于有效的GBM治疗。越来越多的证据表明，以纳米颗粒（NP）形式递送治疗剂可以允许穿过BBB以进行有效的GBM治疗。通过标准乳液法合成桦木酸纳米粒（BA NPs），并通过电子显微镜和动态光散射分析进行表征。通过细胞活力测定、EdU-DNA合成测定、细胞周期测定、线粒体膜电位和PI-FITC凋亡测定来表征所得NP的抗肿瘤作用。通过Western Blot和免疫染色分析进行了进一步的机制研究。最后，我们在颅内异种移植GBM小鼠模型中评估了BA NP的体内药代动力学和抗肿瘤作用。成功地制备了BA纳米颗粒并形成棒状。BA NPs在体外可显著抑制胶质瘤细胞增殖，诱导细胞凋亡，使细胞周期阻滞于G 0/G1期。BA NPs对Akt/NFκB-p65信号通路的抑制作用呈浓度依赖性。我们发现BA纳米粒的抗肿瘤作用依赖于CB 1/CB 2受体的功能。此外，在颅内GBM异种移植小鼠模型中，BA NPs可以有效地穿过血脑屏障，大大延长小鼠的存活时间。我们成功地合成了BA纳米颗粒，它可以穿过血脑屏障，并表现出很强的抗肿瘤作用。因此，BA NP可潜在地用于GBM的有效治疗。在线版本包含补充材料，可通过10.1186/s12951-022-01238-7获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12951-022-01238-7.
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影响因子：
12.4
作者：
Deng, Gang;Ma, Chao;Zhou, Jiangbing
通讯作者：
Zhou, Jiangbing
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影响因子：
4.6
作者：
Lee SY;Kim HH;Park SU
通讯作者：
Park SU
影响因子：
8.4
作者：
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通讯作者：
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影响因子：
8.4
作者：
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通讯作者：
Pezzuto, JM
影响因子：
2.7
作者：
Reitman, Zachary J.;Winkler, Frank;Elia, Andrew E. H.
通讯作者：
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