Delivery of [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] using unfunctionalized and mercapto functionalized SBA-15 mesoporous silica: Preparation, characterization and in vitro study

• Published in: Journal of inorganic biochemistry Vol. 180; pp. 155 - 162
• Main Authors: Edeler, David, Arlt, Sören, Petković, Vladana, Ludwig, Gerd, Drača, Dijana, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Kaluđerović, Goran N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018
• Subjects: Apoptosis; Autophagy; Cytotoxicity; Drug delivery; Ruthenium(II) complex; SBA-15; Ruthenium(II) complex; Cytotoxicity; Drug delivery; SBA-15; Autophagy; Apoptosis
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2017.12.011

SBA-15 (Santa Barbara Amorphous 15) mesoporous silica and its functionalized form (with 3-mercaptopropyltriethoxysilane) SBA-15~SH were used as carriers for [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] complex, denoted as [Ru]. Prepared mesoporous silica nanomaterials were characterized by traditional methods. Materials without [Ru] complex did not show any cytotoxic activity against melanoma B16 and B16-F10 cell lines. On the contrary, materials containing [Ru] such as SBA-15|[Ru] and SBA-15~SH|[Ru], exhibited very high activity against tested tumor cell lines, moreover with similar inhibitory potential. According to the loaded amount of the [Ru] in SBA-15|[Ru] and SBA-15~SH|[Ru] the IC50 values are 1–2μM depending on the test used, thus in comparison to [Ru] alone the activity of nanomaterials containing [Ru] are elevated 3–6 times in vitro. However, the mechanism of apoptosis induction differs for these two mesoporous silica. Unlike reference [Ru] compound and SBA-15~SH|[Ru], SBA-15|[Ru] induces high caspase activation. Discrepancy in mechanism of drugs action at intracellular level points towards an influence of functionalization as well as availability of the drug. Moreover, both SBA-15|[Ru] and SBA-15~SH|[Ru] similarly to [Ru] are declining autophagy in B16 cell line. Nonfunctionalized SBA-15 (Santa Barbara Amorphous 15) mesoporous silica and functionalized with 3-mercaptopropyltriethoxysilane, SBA-15~SH, were used as carriers for [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}], [Ru]. Materials containing [Ru] showed high activity against B16 and B16-F10 cell lines, 3–6 times higher than [Ru]. Apoptosis with suppressed autophagy was detected in B16 cells. [Display omitted] •SBA-15 (Santa Barbara Amorphous 15) mesoporous silica was used as drug carrier.•Its grafted form SBA-15~SH (with 3-mercaptopropyltriethoxysilane) was employed too.•[Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] was loaded into SBA-15 and SBA-15~SH.•Materials with Ru(II) complex were high active against B16 and B16-F10 cells.•Declined autophagy with progressive apoptosis induction in B16 cells treated with materials containing Ru complex was detected.