Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies
CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in l...
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Published in | Journal of inorganic biochemistry Vol. 217; p. 111383 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.04.2021
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Abstract | CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4′,6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2′,7′-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.
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•SBA-15, Santa Barbara amorphous mesoporous silica, was used as carrier for CP, cisplatin.•SBA-15 loaded cisplatin (SBA-15|CP) is equally active on B16F1 cells as CP.•SBA-15|CP induces caspase triggered apoptosis in B16F1 cells.•Senescence is caused through irreversible cell cycle arrest in G2 phase.•SBA-15|CP potently abrogated tumor growth and reduces CP toxicity in vivo. |
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AbstractList | CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4',6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2',7'-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP. CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4′,6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2′,7′-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP. [Display omitted] •SBA-15, Santa Barbara amorphous mesoporous silica, was used as carrier for CP, cisplatin.•SBA-15 loaded cisplatin (SBA-15|CP) is equally active on B16F1 cells as CP.•SBA-15|CP induces caspase triggered apoptosis in B16F1 cells.•Senescence is caused through irreversible cell cycle arrest in G2 phase.•SBA-15|CP potently abrogated tumor growth and reduces CP toxicity in vivo. |
ArticleNumber | 111383 |
Author | Drača, Dijana Dojčinović, Biljana Mijatović, Sanja Maksimović-Ivanić, Danijela Saoud, Mohamad Edeler, David Dunđerović, Duško Đmura, Goran Kaluđerović, Goran N. |
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Keywords | NO SBA-15|CP Drug carrier Cytotoxicity MTT Autophagy DHR FBS RPMI-1640 SBA-15 PBS DAF FM DAPI CFSE B16F1 MCM-41 EDTA CP Cisplatin AO SA-β-Gal CV ROS PI Apoptosis SBA-15p |
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Snippet | CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic... |
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SubjectTerms | Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Apoptosis - drug effects Autophagy Autophagy - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cisplatin Cisplatin - pharmacology Cisplatin - therapeutic use Cytotoxicity Drug carrier Drug Carriers - chemistry Female G2 Phase Cell Cycle Checkpoints - drug effects Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Nanoparticles - chemistry Nitric Oxide - metabolism Porosity SBA-15 Silicon Dioxide - chemistry |
Title | Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies |
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