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

Dijana Drača; David Edeler; Mohamad Saoud; Biljana Dojčinović; Duško Dunđerović; Goran Đmura; Danijela Maksimović-Ivanić; Sanja Mijatović; Goran N Kaluđerović

doi:10.1016/j.jinorgbio.2021.111383

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

J Inorg Biochem. 2021 Apr:217:111383. doi: 10.1016/j.jinorgbio.2021.111383. Epub 2021 Feb 3.

Authors

Dijana Drača¹, David Edeler², Mohamad Saoud², Biljana Dojčinović³, Duško Dunđerović⁴, Goran Đmura⁵, Danijela Maksimović-Ivanić¹, Sanja Mijatović¹, Goran N Kaluđerović⁶

Affiliations

¹ Department of Immunology, Institute for Biological Research"Siniša Stanković" National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
² Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale), Germany.
³ University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Njegoševa 12, 11000 Belgrade, Serbia.
⁴ Institute of Pathology, School of Medicine, University of Belgrade, dr Subotića 1, 11000 Belgrade, Serbia.
⁵ Animal Facility, Institute for Biological Research"Siniša Stanković" National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
⁶ Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale), Germany; Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, DE-06217 Merseburg, Germany. Electronic address: goran.kaluderovic@hs-merseburg.de.

PMID: 33582397
DOI: 10.1016/j.jinorgbio.2021.111383

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.

Keywords: Apoptosis; Autophagy; Cisplatin; Cytotoxicity; Drug carrier; SBA-15.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Apoptosis / drug effects
Autophagy / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology
Cisplatin / therapeutic use*
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
Silicon Dioxide / chemistry*

Substances

Antineoplastic Agents
Drug Carriers
SBA-15
Nitric Oxide
Silicon Dioxide
Cisplatin