Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities
Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensit...
Ausführliche Beschreibung
Autor*in: |
Shi, Yongli [verfasserIn] |
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E-Artikel |
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Englisch |
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2022transfer abstract |
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Enthalten in: Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills - Han, Zhe ELSEVIER, 2019, an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, Amsterdam [u.a.] |
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Übergeordnetes Werk: |
volume:220 ; year:2022 ; pages:0 |
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DOI / URN: |
10.1016/j.colsurfb.2022.112874 |
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ELV059640332 |
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245 | 1 | 0 | |a Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities |
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520 | |a Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. | ||
520 | |a Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. | ||
650 | 7 | |a Nanoparticles |2 Elsevier | |
650 | 7 | |a in vivo toxicity |2 Elsevier | |
650 | 7 | |a GSH-responsibility |2 Elsevier | |
650 | 7 | |a Anti-tumor |2 Elsevier | |
650 | 7 | |a 4T1 cells |2 Elsevier | |
650 | 7 | |a DOX |2 Elsevier | |
700 | 1 | |a Hou, Xueyan |4 oth | |
700 | 1 | |a Yu, ShaSha |4 oth | |
700 | 1 | |a Pan, Xiaofei |4 oth | |
700 | 1 | |a Yang, Mingbo |4 oth | |
700 | 1 | |a Hu, Jie |4 oth | |
700 | 1 | |a Wang, Xiao |4 oth | |
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10.1016/j.colsurfb.2022.112874 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001978.pica (DE-627)ELV059640332 (ELSEVIER)S0927-7765(22)00558-6 DE-627 ger DE-627 rakwb eng 540 VZ Shi, Yongli verfasserin aut Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities 2022transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Nanoparticles Elsevier in vivo toxicity Elsevier GSH-responsibility Elsevier Anti-tumor Elsevier 4T1 cells Elsevier DOX Elsevier Hou, Xueyan oth Yu, ShaSha oth Pan, Xiaofei oth Yang, Mingbo oth Hu, Jie oth Wang, Xiao oth Enthalten in Elsevier Science Han, Zhe ELSEVIER Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills 2019 an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin Amsterdam [u.a.] (DE-627)ELV003763382 volume:220 year:2022 pages:0 https://doi.org/10.1016/j.colsurfb.2022.112874 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA AR 220 2022 0 |
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10.1016/j.colsurfb.2022.112874 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001978.pica (DE-627)ELV059640332 (ELSEVIER)S0927-7765(22)00558-6 DE-627 ger DE-627 rakwb eng 540 VZ Shi, Yongli verfasserin aut Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities 2022transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Nanoparticles Elsevier in vivo toxicity Elsevier GSH-responsibility Elsevier Anti-tumor Elsevier 4T1 cells Elsevier DOX Elsevier Hou, Xueyan oth Yu, ShaSha oth Pan, Xiaofei oth Yang, Mingbo oth Hu, Jie oth Wang, Xiao oth Enthalten in Elsevier Science Han, Zhe ELSEVIER Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills 2019 an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin Amsterdam [u.a.] (DE-627)ELV003763382 volume:220 year:2022 pages:0 https://doi.org/10.1016/j.colsurfb.2022.112874 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA AR 220 2022 0 |
allfields_unstemmed |
10.1016/j.colsurfb.2022.112874 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001978.pica (DE-627)ELV059640332 (ELSEVIER)S0927-7765(22)00558-6 DE-627 ger DE-627 rakwb eng 540 VZ Shi, Yongli verfasserin aut Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities 2022transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Nanoparticles Elsevier in vivo toxicity Elsevier GSH-responsibility Elsevier Anti-tumor Elsevier 4T1 cells Elsevier DOX Elsevier Hou, Xueyan oth Yu, ShaSha oth Pan, Xiaofei oth Yang, Mingbo oth Hu, Jie oth Wang, Xiao oth Enthalten in Elsevier Science Han, Zhe ELSEVIER Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills 2019 an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin Amsterdam [u.a.] (DE-627)ELV003763382 volume:220 year:2022 pages:0 https://doi.org/10.1016/j.colsurfb.2022.112874 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA AR 220 2022 0 |
allfieldsGer |
10.1016/j.colsurfb.2022.112874 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001978.pica (DE-627)ELV059640332 (ELSEVIER)S0927-7765(22)00558-6 DE-627 ger DE-627 rakwb eng 540 VZ Shi, Yongli verfasserin aut Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities 2022transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Nanoparticles Elsevier in vivo toxicity Elsevier GSH-responsibility Elsevier Anti-tumor Elsevier 4T1 cells Elsevier DOX Elsevier Hou, Xueyan oth Yu, ShaSha oth Pan, Xiaofei oth Yang, Mingbo oth Hu, Jie oth Wang, Xiao oth Enthalten in Elsevier Science Han, Zhe ELSEVIER Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills 2019 an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin Amsterdam [u.a.] (DE-627)ELV003763382 volume:220 year:2022 pages:0 https://doi.org/10.1016/j.colsurfb.2022.112874 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA AR 220 2022 0 |
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10.1016/j.colsurfb.2022.112874 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001978.pica (DE-627)ELV059640332 (ELSEVIER)S0927-7765(22)00558-6 DE-627 ger DE-627 rakwb eng 540 VZ Shi, Yongli verfasserin aut Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities 2022transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. Nanoparticles Elsevier in vivo toxicity Elsevier GSH-responsibility Elsevier Anti-tumor Elsevier 4T1 cells Elsevier DOX Elsevier Hou, Xueyan oth Yu, ShaSha oth Pan, Xiaofei oth Yang, Mingbo oth Hu, Jie oth Wang, Xiao oth Enthalten in Elsevier Science Han, Zhe ELSEVIER Pharmacy students' perceptions toward peer assessment and its use in teaching patient presentation skills 2019 an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin Amsterdam [u.a.] (DE-627)ELV003763382 volume:220 year:2022 pages:0 https://doi.org/10.1016/j.colsurfb.2022.112874 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA AR 220 2022 0 |
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Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities |
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Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. |
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Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. |
abstract_unstemmed |
Doxorubicin (DOX) is widely used in the treatment of many tumors, but the dose-dependent toxicity limits its further application. In this study, a unique strategy was developed to improve the anti-tumor effects of free DOX and lower its in vivo toxicity by constructing novel glutathione (GSH)-sensitive poloxamer188-b-polycaprolactone-S-S-doxorubicin nanoparticles (PPSSD NPs). After uptake by tumor cells, the disulfide bonds in the PPSSD NPs would be cloven by reacting with GSH. Then, a lethal dose of DOX was released in tumor cells. The uptake of PPSSD NPs by 4T1 cells was proved using fluorescence microscopy by co-localization of PPSSD NPs and 4′, 6-diamidino-2-phenylindole (DAPI). Cell tests suggested that the PPSSD NPs showed high anti-tumor cells (4T1) activity but low cytotoxicity against normal cells (293 t). The in vivo toxicity and anti-tumor effects of the PPSSD NPs were studied with Kunming and Balb/c mice as models, respectively. The H&E slices, blood routine and biochemistry indexes of the PPSSD NPs treated mice indicated that the PPSSD NPs did not induce obvious in vivo toxicity. The PPSSD NPs showed higher in vitro anti-4T1 cells activity than free DOX. Furthermore, the in vivo anti-tumor study, TUNEL and H&E slices suggested that the PPSSD NPs exhibited excellent anti-tumor effects. In a word, the novel PPSSD NPs did not only improve the anti-tumor effect of DOX, but also decrease its cytotoxicity to normal tissues. |
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Targeted delivery of doxorubicin into tumor cells to decrease the in vivo toxicity of glutathione-sensitive prodrug-poloxamer188-b-polycaprolactone nanoparticles and improve their anti-tumor activities |
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