Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel
The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delive...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Lv, Shixian [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014transfer abstract |
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| Umfang: |
8 |
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| Übergeordnetes Werk: |
Enthalten in: 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up - Moschini, M. ELSEVIER, 2015, official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems, New York, NY [u.a.] |
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| Übergeordnetes Werk: |
volume:194 ; year:2014 ; day:28 ; month:11 ; pages:220-227 ; extent:8 |
| Links: |
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| DOI / URN: |
10.1016/j.jconrel.2014.09.009 |
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ELV039237818 |
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| 245 | 1 | 0 | |a Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel |
| 264 | 1 | |c 2014transfer abstract | |
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| 520 | |a The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. | ||
| 520 | |a The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. | ||
| 700 | 1 | |a Tang, Zhaohui |4 oth | |
| 700 | 1 | |a Zhang, Dawei |4 oth | |
| 700 | 1 | |a Song, Wantong |4 oth | |
| 700 | 1 | |a Li, Mingqiang |4 oth | |
| 700 | 1 | |a Lin, Jian |4 oth | |
| 700 | 1 | |a Liu, Huaiyu |4 oth | |
| 700 | 1 | |a Chen, Xuesi |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Moschini, M. ELSEVIER |t 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up |d 2015 |d official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems |g New York, NY [u.a.] |w (DE-627)ELV012920894 |
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10.1016/j.jconrel.2014.09.009 doi GBVA2014005000025.pica (DE-627)ELV039237818 (ELSEVIER)S0168-3659(14)00638-5 DE-627 ger DE-627 rakwb eng 540 610 540 DE-600 610 DE-600 610 VZ 670 VZ 35.80 bkl Lv, Shixian verfasserin aut Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. Tang, Zhaohui oth Zhang, Dawei oth Song, Wantong oth Li, Mingqiang oth Lin, Jian oth Liu, Huaiyu oth Chen, Xuesi oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 https://doi.org/10.1016/j.jconrel.2014.09.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 194 2014 28 1128 220-227 8 045F 540 |
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10.1016/j.jconrel.2014.09.009 doi GBVA2014005000025.pica (DE-627)ELV039237818 (ELSEVIER)S0168-3659(14)00638-5 DE-627 ger DE-627 rakwb eng 540 610 540 DE-600 610 DE-600 610 VZ 670 VZ 35.80 bkl Lv, Shixian verfasserin aut Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. Tang, Zhaohui oth Zhang, Dawei oth Song, Wantong oth Li, Mingqiang oth Lin, Jian oth Liu, Huaiyu oth Chen, Xuesi oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 https://doi.org/10.1016/j.jconrel.2014.09.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 194 2014 28 1128 220-227 8 045F 540 |
| allfields_unstemmed |
10.1016/j.jconrel.2014.09.009 doi GBVA2014005000025.pica (DE-627)ELV039237818 (ELSEVIER)S0168-3659(14)00638-5 DE-627 ger DE-627 rakwb eng 540 610 540 DE-600 610 DE-600 610 VZ 670 VZ 35.80 bkl Lv, Shixian verfasserin aut Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. Tang, Zhaohui oth Zhang, Dawei oth Song, Wantong oth Li, Mingqiang oth Lin, Jian oth Liu, Huaiyu oth Chen, Xuesi oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 https://doi.org/10.1016/j.jconrel.2014.09.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 194 2014 28 1128 220-227 8 045F 540 |
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10.1016/j.jconrel.2014.09.009 doi GBVA2014005000025.pica (DE-627)ELV039237818 (ELSEVIER)S0168-3659(14)00638-5 DE-627 ger DE-627 rakwb eng 540 610 540 DE-600 610 DE-600 610 VZ 670 VZ 35.80 bkl Lv, Shixian verfasserin aut Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. Tang, Zhaohui oth Zhang, Dawei oth Song, Wantong oth Li, Mingqiang oth Lin, Jian oth Liu, Huaiyu oth Chen, Xuesi oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 https://doi.org/10.1016/j.jconrel.2014.09.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 194 2014 28 1128 220-227 8 045F 540 |
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10.1016/j.jconrel.2014.09.009 doi GBVA2014005000025.pica (DE-627)ELV039237818 (ELSEVIER)S0168-3659(14)00638-5 DE-627 ger DE-627 rakwb eng 540 610 540 DE-600 610 DE-600 610 VZ 670 VZ 35.80 bkl Lv, Shixian verfasserin aut Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel 2014transfer abstract 8 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. Tang, Zhaohui oth Zhang, Dawei oth Song, Wantong oth Li, Mingqiang oth Lin, Jian oth Liu, Huaiyu oth Chen, Xuesi oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 https://doi.org/10.1016/j.jconrel.2014.09.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 194 2014 28 1128 220-227 8 045F 540 |
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Enthalten in 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up New York, NY [u.a.] volume:194 year:2014 day:28 month:11 pages:220-227 extent:8 |
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537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up |
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Lv, Shixian @@aut@@ Tang, Zhaohui @@oth@@ Zhang, Dawei @@oth@@ Song, Wantong @@oth@@ Li, Mingqiang @@oth@@ Lin, Jian @@oth@@ Liu, Huaiyu @@oth@@ Chen, Xuesi @@oth@@ |
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Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel |
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The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. |
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The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. |
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The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. |
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A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG-b-P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH≈5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tang, Zhaohui</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhang, Dawei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Song, Wantong</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Mingqiang</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lin, Jian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Huaiyu</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Xuesi</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Moschini, M. ELSEVIER</subfield><subfield code="t">537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up</subfield><subfield code="d">2015</subfield><subfield code="d">official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV012920894</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:194</subfield><subfield code="g">year:2014</subfield><subfield code="g">day:28</subfield><subfield code="g">month:11</subfield><subfield code="g">pages:220-227</subfield><subfield code="g">extent:8</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.jconrel.2014.09.009</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">35.80</subfield><subfield code="j">Makromolekulare Chemie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">194</subfield><subfield code="j">2014</subfield><subfield code="b">28</subfield><subfield code="c">1128</subfield><subfield code="h">220-227</subfield><subfield code="g">8</subfield></datafield><datafield tag="953" ind1=" " ind2=" "><subfield code="2">045F</subfield><subfield code="a">540</subfield></datafield></record></collection>
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