Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best...
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Autor*in:	Lisa Gherardini [verfasserIn] Veronica Vetri Buratti [verfasserIn] Mirko Maturi [verfasserIn] Giovanni Inzalaco [verfasserIn] Erica Locatelli [verfasserIn] Letizia Sambri [verfasserIn] Sara Gargiulo [verfasserIn] Virginia Barone [verfasserIn] Denise Bonente [verfasserIn] Eugenio Bertelli [verfasserIn] Silvia Tortorella [verfasserIn] Lorenzo Franci [verfasserIn] Antonio Fioravanti [verfasserIn] Mauro Comes Franchini [verfasserIn] Mario Chiariello [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 13(2023), 1, Seite 15
Übergeordnetes Werk:	volume:13 ; year:2023 ; number:1 ; pages:15

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-023-31811-5

Katalog-ID:	DOAJ087744295

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allfields	10.1038/s41598-023-31811-5 doi (DE-627)DOAJ087744295 (DE-599)DOAJa673b4ee4c384c1aae31d45e333b78fc DE-627 ger DE-627 rakwb eng Lisa Gherardini verfasserin aut Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM. Medicine R Science Q Veronica Vetri Buratti verfasserin aut Mirko Maturi verfasserin aut Giovanni Inzalaco verfasserin aut Erica Locatelli verfasserin aut Letizia Sambri verfasserin aut Sara Gargiulo verfasserin aut Virginia Barone verfasserin aut Denise Bonente verfasserin aut Eugenio Bertelli verfasserin aut Silvia Tortorella verfasserin aut Lorenzo Franci verfasserin aut Antonio Fioravanti verfasserin aut Mauro Comes Franchini verfasserin aut Mario Chiariello verfasserin aut In Scientific Reports Nature Portfolio, 2011 13(2023), 1, Seite 15 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:13 year:2023 number:1 pages:15 https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc kostenfrei https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 1 15
spelling	10.1038/s41598-023-31811-5 doi (DE-627)DOAJ087744295 (DE-599)DOAJa673b4ee4c384c1aae31d45e333b78fc DE-627 ger DE-627 rakwb eng Lisa Gherardini verfasserin aut Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM. Medicine R Science Q Veronica Vetri Buratti verfasserin aut Mirko Maturi verfasserin aut Giovanni Inzalaco verfasserin aut Erica Locatelli verfasserin aut Letizia Sambri verfasserin aut Sara Gargiulo verfasserin aut Virginia Barone verfasserin aut Denise Bonente verfasserin aut Eugenio Bertelli verfasserin aut Silvia Tortorella verfasserin aut Lorenzo Franci verfasserin aut Antonio Fioravanti verfasserin aut Mauro Comes Franchini verfasserin aut Mario Chiariello verfasserin aut In Scientific Reports Nature Portfolio, 2011 13(2023), 1, Seite 15 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:13 year:2023 number:1 pages:15 https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc kostenfrei https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 1 15
allfields_unstemmed	10.1038/s41598-023-31811-5 doi (DE-627)DOAJ087744295 (DE-599)DOAJa673b4ee4c384c1aae31d45e333b78fc DE-627 ger DE-627 rakwb eng Lisa Gherardini verfasserin aut Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM. Medicine R Science Q Veronica Vetri Buratti verfasserin aut Mirko Maturi verfasserin aut Giovanni Inzalaco verfasserin aut Erica Locatelli verfasserin aut Letizia Sambri verfasserin aut Sara Gargiulo verfasserin aut Virginia Barone verfasserin aut Denise Bonente verfasserin aut Eugenio Bertelli verfasserin aut Silvia Tortorella verfasserin aut Lorenzo Franci verfasserin aut Antonio Fioravanti verfasserin aut Mauro Comes Franchini verfasserin aut Mario Chiariello verfasserin aut In Scientific Reports Nature Portfolio, 2011 13(2023), 1, Seite 15 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:13 year:2023 number:1 pages:15 https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc kostenfrei https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 1 15
allfieldsGer	10.1038/s41598-023-31811-5 doi (DE-627)DOAJ087744295 (DE-599)DOAJa673b4ee4c384c1aae31d45e333b78fc DE-627 ger DE-627 rakwb eng Lisa Gherardini verfasserin aut Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM. Medicine R Science Q Veronica Vetri Buratti verfasserin aut Mirko Maturi verfasserin aut Giovanni Inzalaco verfasserin aut Erica Locatelli verfasserin aut Letizia Sambri verfasserin aut Sara Gargiulo verfasserin aut Virginia Barone verfasserin aut Denise Bonente verfasserin aut Eugenio Bertelli verfasserin aut Silvia Tortorella verfasserin aut Lorenzo Franci verfasserin aut Antonio Fioravanti verfasserin aut Mauro Comes Franchini verfasserin aut Mario Chiariello verfasserin aut In Scientific Reports Nature Portfolio, 2011 13(2023), 1, Seite 15 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:13 year:2023 number:1 pages:15 https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc kostenfrei https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 1 15
allfieldsSound	10.1038/s41598-023-31811-5 doi (DE-627)DOAJ087744295 (DE-599)DOAJa673b4ee4c384c1aae31d45e333b78fc DE-627 ger DE-627 rakwb eng Lisa Gherardini verfasserin aut Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM. Medicine R Science Q Veronica Vetri Buratti verfasserin aut Mirko Maturi verfasserin aut Giovanni Inzalaco verfasserin aut Erica Locatelli verfasserin aut Letizia Sambri verfasserin aut Sara Gargiulo verfasserin aut Virginia Barone verfasserin aut Denise Bonente verfasserin aut Eugenio Bertelli verfasserin aut Silvia Tortorella verfasserin aut Lorenzo Franci verfasserin aut Antonio Fioravanti verfasserin aut Mauro Comes Franchini verfasserin aut Mario Chiariello verfasserin aut In Scientific Reports Nature Portfolio, 2011 13(2023), 1, Seite 15 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:13 year:2023 number:1 pages:15 https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc kostenfrei https://doi.org/10.1038/s41598-023-31811-5 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 1 15
language	English
source	In Scientific Reports 13(2023), 1, Seite 15 volume:13 year:2023 number:1 pages:15
sourceStr	In Scientific Reports 13(2023), 1, Seite 15 volume:13 year:2023 number:1 pages:15
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	Scientific Reports
authorswithroles_txt_mv	Lisa Gherardini @@aut@@ Veronica Vetri Buratti @@aut@@ Mirko Maturi @@aut@@ Giovanni Inzalaco @@aut@@ Erica Locatelli @@aut@@ Letizia Sambri @@aut@@ Sara Gargiulo @@aut@@ Virginia Barone @@aut@@ Denise Bonente @@aut@@ Eugenio Bertelli @@aut@@ Silvia Tortorella @@aut@@ Lorenzo Franci @@aut@@ Antonio Fioravanti @@aut@@ Mauro Comes Franchini @@aut@@ Mario Chiariello @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ087744295
language_de	englisch
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author	Lisa Gherardini
spellingShingle	Lisa Gherardini misc Medicine misc R misc Science misc Q Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
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topic_title	Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
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title	Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
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title_full	Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
author_sort	Lisa Gherardini
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author_browse	Lisa Gherardini Veronica Vetri Buratti Mirko Maturi Giovanni Inzalaco Erica Locatelli Letizia Sambri Sara Gargiulo Virginia Barone Denise Bonente Eugenio Bertelli Silvia Tortorella Lorenzo Franci Antonio Fioravanti Mauro Comes Franchini Mario Chiariello
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title_sort	loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
title_auth	Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
abstract	Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.
abstractGer	Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.
abstract_unstemmed	Abstract Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THGSiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.
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title_short	Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models
url	https://doi.org/10.1038/s41598-023-31811-5 https://doaj.org/article/a673b4ee4c384c1aae31d45e333b78fc https://doaj.org/toc/2045-2322
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Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

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