Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies

• Published in: Journal of inorganic biochemistry Vol. 217; p. 111383
• Main Authors: Drača, Dijana, Edeler, David, Saoud, Mohamad, Dojčinović, Biljana, Dunđerović, Duško, Đmura, Goran, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Kaluđerović, Goran N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2021
• Subjects: 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; 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
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111383

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.