Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma

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. Ac...
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Autor*in:	Li, Yong [verfasserIn] 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

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Betulinic acid Nanoparticles Proliferation Apoptosis CB1/CB2

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Journal of nanobiotechnology - London : Biomed Central, 2003, 20(2022), 1 vom: 21. Jan.
Übergeordnetes Werk:	volume:20 ; year:2022 ; number:1 ; day:21 ; month:01

Links:	Volltext

DOI / URN:	10.1186/s12951-022-01238-7

Katalog-ID:	SPR050431471

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520			\|a 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. Graphical Abstract
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allfields	10.1186/s12951-022-01238-7 doi (DE-627)SPR050431471 (SPR)s12951-022-01238-7-e DE-627 ger DE-627 rakwb eng Li, Yong verfasserin aut Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Graphical Abstract Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213 Wang, Yixuan aut Gao, Lun aut Tan, Yinqiu aut Cai, Jiayang aut Ye, Zhang aut Chen, Ann T. aut Xu, Yang aut Zhao, Linyao aut Tong, Shiao aut Sun, Qian aut Liu, Baohui aut Zhang, Shenqi aut Tian, Daofeng aut Deng, Gang aut Zhou, Jiangbing aut Chen, Qianxue (orcid)0000-0002-9413-1030 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 21. Jan. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:21 month:01 https://dx.doi.org/10.1186/s12951-022-01238-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 21 01
spelling	10.1186/s12951-022-01238-7 doi (DE-627)SPR050431471 (SPR)s12951-022-01238-7-e DE-627 ger DE-627 rakwb eng Li, Yong verfasserin aut Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Graphical Abstract Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213 Wang, Yixuan aut Gao, Lun aut Tan, Yinqiu aut Cai, Jiayang aut Ye, Zhang aut Chen, Ann T. aut Xu, Yang aut Zhao, Linyao aut Tong, Shiao aut Sun, Qian aut Liu, Baohui aut Zhang, Shenqi aut Tian, Daofeng aut Deng, Gang aut Zhou, Jiangbing aut Chen, Qianxue (orcid)0000-0002-9413-1030 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 21. Jan. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:21 month:01 https://dx.doi.org/10.1186/s12951-022-01238-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 21 01
allfields_unstemmed	10.1186/s12951-022-01238-7 doi (DE-627)SPR050431471 (SPR)s12951-022-01238-7-e DE-627 ger DE-627 rakwb eng Li, Yong verfasserin aut Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Graphical Abstract Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213 Wang, Yixuan aut Gao, Lun aut Tan, Yinqiu aut Cai, Jiayang aut Ye, Zhang aut Chen, Ann T. aut Xu, Yang aut Zhao, Linyao aut Tong, Shiao aut Sun, Qian aut Liu, Baohui aut Zhang, Shenqi aut Tian, Daofeng aut Deng, Gang aut Zhou, Jiangbing aut Chen, Qianxue (orcid)0000-0002-9413-1030 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 21. Jan. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:21 month:01 https://dx.doi.org/10.1186/s12951-022-01238-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 21 01
allfieldsGer	10.1186/s12951-022-01238-7 doi (DE-627)SPR050431471 (SPR)s12951-022-01238-7-e DE-627 ger DE-627 rakwb eng Li, Yong verfasserin aut Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Graphical Abstract Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213 Wang, Yixuan aut Gao, Lun aut Tan, Yinqiu aut Cai, Jiayang aut Ye, Zhang aut Chen, Ann T. aut Xu, Yang aut Zhao, Linyao aut Tong, Shiao aut Sun, Qian aut Liu, Baohui aut Zhang, Shenqi aut Tian, Daofeng aut Deng, Gang aut Zhou, Jiangbing aut Chen, Qianxue (orcid)0000-0002-9413-1030 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 21. Jan. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:21 month:01 https://dx.doi.org/10.1186/s12951-022-01238-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 21 01
allfieldsSound	10.1186/s12951-022-01238-7 doi (DE-627)SPR050431471 (SPR)s12951-022-01238-7-e DE-627 ger DE-627 rakwb eng Li, Yong verfasserin aut Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Graphical Abstract Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213 Wang, Yixuan aut Gao, Lun aut Tan, Yinqiu aut Cai, Jiayang aut Ye, Zhang aut Chen, Ann T. aut Xu, Yang aut Zhao, Linyao aut Tong, Shiao aut Sun, Qian aut Liu, Baohui aut Zhang, Shenqi aut Tian, Daofeng aut Deng, Gang aut Zhou, Jiangbing aut Chen, Qianxue (orcid)0000-0002-9413-1030 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 21. Jan. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:21 month:01 https://dx.doi.org/10.1186/s12951-022-01238-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2022 1 21 01
language	English
source	Enthalten in Journal of nanobiotechnology 20(2022), 1 vom: 21. Jan. volume:20 year:2022 number:1 day:21 month:01
sourceStr	Enthalten in Journal of nanobiotechnology 20(2022), 1 vom: 21. Jan. volume:20 year:2022 number:1 day:21 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Betulinic acid Nanoparticles Proliferation Apoptosis CB1/CB2
isfreeaccess_bool	true
container_title	Journal of nanobiotechnology
authorswithroles_txt_mv	Li, Yong @@aut@@ Wang, Yixuan @@aut@@ Gao, Lun @@aut@@ Tan, Yinqiu @@aut@@ Cai, Jiayang @@aut@@ Ye, Zhang @@aut@@ Chen, Ann T. @@aut@@ Xu, Yang @@aut@@ Zhao, Linyao @@aut@@ Tong, Shiao @@aut@@ Sun, Qian @@aut@@ Liu, Baohui @@aut@@ Zhang, Shenqi @@aut@@ Tian, Daofeng @@aut@@ Deng, Gang @@aut@@ Zhou, Jiangbing @@aut@@ Chen, Qianxue @@aut@@
publishDateDaySort_date	2022-01-21T00:00:00Z
hierarchy_top_id	362770328
id	SPR050431471
language_de	englisch
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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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author	Li, Yong
spellingShingle	Li, Yong misc Betulinic acid misc Nanoparticles misc Proliferation misc Apoptosis misc CB1/CB2 Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
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topic_title	Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma Betulinic acid (dpeaa)DE-He213 Nanoparticles (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 CB1/CB2 (dpeaa)DE-He213
topic	misc Betulinic acid misc Nanoparticles misc Proliferation misc Apoptosis misc CB1/CB2
topic_unstemmed	misc Betulinic acid misc Nanoparticles misc Proliferation misc Apoptosis misc CB1/CB2
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title	Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
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title_full	Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
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author_browse	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
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title_sort	betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
title_auth	Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
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. Graphical Abstract © The Author(s) 2022
abstractGer	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. Graphical Abstract © The Author(s) 2022
abstract_unstemmed	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. Graphical Abstract © The Author(s) 2022
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title_short	Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma
url	https://dx.doi.org/10.1186/s12951-022-01238-7
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author2	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
author2Str	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
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up_date	2024-07-03T15:30:07.903Z
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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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