Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic>
Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanopart...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kozielski, Kristen L. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019transfer abstract |
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| Schlagwörter: |
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| Umfang: |
9 |
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| Übergeordnetes Werk: |
Enthalten in: Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field - 2012, biomaterials reviews online, Amsterdam [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:209 ; year:2019 ; pages:79-87 ; extent:9 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.biomaterials.2019.04.020 |
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ELV046703446 |
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| 245 | 1 | 0 | |a Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> |
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| 520 | |a Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. | ||
| 520 | |a Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. | ||
| 650 | 7 | |a Nanoparticle |2 Elsevier | |
| 650 | 7 | |a Cancer therapy |2 Elsevier | |
| 650 | 7 | |a siRNA |2 Elsevier | |
| 650 | 7 | |a Combination therapy |2 Elsevier | |
| 650 | 7 | |a Gene therapy |2 Elsevier | |
| 700 | 1 | |a Ruiz-Valls, Alejandro |4 oth | |
| 700 | 1 | |a Tzeng, Stephany Y. |4 oth | |
| 700 | 1 | |a Guerrero-Cázares, Hugo |4 oth | |
| 700 | 1 | |a Rui, Yuan |4 oth | |
| 700 | 1 | |a Li, Yuxin |4 oth | |
| 700 | 1 | |a Vaughan, Hannah J. |4 oth | |
| 700 | 1 | |a Gionet-Gonzales, Marissa |4 oth | |
| 700 | 1 | |a Vantucci, Casey |4 oth | |
| 700 | 1 | |a Kim, Jayoung |4 oth | |
| 700 | 1 | |a Schiapparelli, Paula |4 oth | |
| 700 | 1 | |a Al-Kharboosh, Rawan |4 oth | |
| 700 | 1 | |a Quiñones-Hinojosa, Alfredo |4 oth | |
| 700 | 1 | |a Green, Jordan J. |4 oth | |
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10.1016/j.biomaterials.2019.04.020 doi GBV00000000000615.pica (DE-627)ELV046703446 (ELSEVIER)S0142-9612(19)30237-6 DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Kozielski, Kristen L. verfasserin aut Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> 2019transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Nanoparticle Elsevier Cancer therapy Elsevier siRNA Elsevier Combination therapy Elsevier Gene therapy Elsevier Ruiz-Valls, Alejandro oth Tzeng, Stephany Y. oth Guerrero-Cázares, Hugo oth Rui, Yuan oth Li, Yuxin oth Vaughan, Hannah J. oth Gionet-Gonzales, Marissa oth Vantucci, Casey oth Kim, Jayoung oth Schiapparelli, Paula oth Al-Kharboosh, Rawan oth Quiñones-Hinojosa, Alfredo oth Green, Jordan J. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:209 year:2019 pages:79-87 extent:9 https://doi.org/10.1016/j.biomaterials.2019.04.020 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 209 2019 79-87 9 |
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10.1016/j.biomaterials.2019.04.020 doi GBV00000000000615.pica (DE-627)ELV046703446 (ELSEVIER)S0142-9612(19)30237-6 DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Kozielski, Kristen L. verfasserin aut Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> 2019transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Nanoparticle Elsevier Cancer therapy Elsevier siRNA Elsevier Combination therapy Elsevier Gene therapy Elsevier Ruiz-Valls, Alejandro oth Tzeng, Stephany Y. oth Guerrero-Cázares, Hugo oth Rui, Yuan oth Li, Yuxin oth Vaughan, Hannah J. oth Gionet-Gonzales, Marissa oth Vantucci, Casey oth Kim, Jayoung oth Schiapparelli, Paula oth Al-Kharboosh, Rawan oth Quiñones-Hinojosa, Alfredo oth Green, Jordan J. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:209 year:2019 pages:79-87 extent:9 https://doi.org/10.1016/j.biomaterials.2019.04.020 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 209 2019 79-87 9 |
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10.1016/j.biomaterials.2019.04.020 doi GBV00000000000615.pica (DE-627)ELV046703446 (ELSEVIER)S0142-9612(19)30237-6 DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Kozielski, Kristen L. verfasserin aut Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> 2019transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Nanoparticle Elsevier Cancer therapy Elsevier siRNA Elsevier Combination therapy Elsevier Gene therapy Elsevier Ruiz-Valls, Alejandro oth Tzeng, Stephany Y. oth Guerrero-Cázares, Hugo oth Rui, Yuan oth Li, Yuxin oth Vaughan, Hannah J. oth Gionet-Gonzales, Marissa oth Vantucci, Casey oth Kim, Jayoung oth Schiapparelli, Paula oth Al-Kharboosh, Rawan oth Quiñones-Hinojosa, Alfredo oth Green, Jordan J. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:209 year:2019 pages:79-87 extent:9 https://doi.org/10.1016/j.biomaterials.2019.04.020 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 209 2019 79-87 9 |
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10.1016/j.biomaterials.2019.04.020 doi GBV00000000000615.pica (DE-627)ELV046703446 (ELSEVIER)S0142-9612(19)30237-6 DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Kozielski, Kristen L. verfasserin aut Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> 2019transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Nanoparticle Elsevier Cancer therapy Elsevier siRNA Elsevier Combination therapy Elsevier Gene therapy Elsevier Ruiz-Valls, Alejandro oth Tzeng, Stephany Y. oth Guerrero-Cázares, Hugo oth Rui, Yuan oth Li, Yuxin oth Vaughan, Hannah J. oth Gionet-Gonzales, Marissa oth Vantucci, Casey oth Kim, Jayoung oth Schiapparelli, Paula oth Al-Kharboosh, Rawan oth Quiñones-Hinojosa, Alfredo oth Green, Jordan J. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:209 year:2019 pages:79-87 extent:9 https://doi.org/10.1016/j.biomaterials.2019.04.020 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 209 2019 79-87 9 |
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10.1016/j.biomaterials.2019.04.020 doi GBV00000000000615.pica (DE-627)ELV046703446 (ELSEVIER)S0142-9612(19)30237-6 DE-627 ger DE-627 rakwb eng 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Kozielski, Kristen L. verfasserin aut Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> 2019transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. Nanoparticle Elsevier Cancer therapy Elsevier siRNA Elsevier Combination therapy Elsevier Gene therapy Elsevier Ruiz-Valls, Alejandro oth Tzeng, Stephany Y. oth Guerrero-Cázares, Hugo oth Rui, Yuan oth Li, Yuxin oth Vaughan, Hannah J. oth Gionet-Gonzales, Marissa oth Vantucci, Casey oth Kim, Jayoung oth Schiapparelli, Paula oth Al-Kharboosh, Rawan oth Quiñones-Hinojosa, Alfredo oth Green, Jordan J. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:209 year:2019 pages:79-87 extent:9 https://doi.org/10.1016/j.biomaterials.2019.04.020 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 209 2019 79-87 9 |
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cancer-selective nanoparticles for combinatorial sirna delivery to primary human gbm <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> |
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Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> |
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Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. |
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Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. |
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Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer. |
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Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> |
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We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells’ ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. 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