Effect of chain length on the cytotoxic activity of (alkyl-ω-ol)triphenyltin(IV) loaded into SBA-15 nanostructured silica and in vivo study of SBA-15~Cl|Ph3Sn(CH2)8OH
Goran N Kalu?erovi?, Christian Bensing, Marija Moji?, Mirna Bulatovi? et. al.
Abstract
A series of nanostructured SBA-15-based materials functionalized with the tetraorganotin(IV) metallodrugs Ph3Sn(CH2)nOH (n = 3, 4, 6, 8 and 11) are synthesized and structurally characterized by different techniques used in solid-state chemistry. The cytotoxicity of both the organotin(IV) compounds and the tin-functionalized SBA-15 materials are studied against different cancer cell lines observing that the materials have similar cytotoxic activity in comparison with the free organotin compounds in terms of mass. However, considering that the percentage of active metal compound loaded into material is low, the utilization of mesoporous silica as drug vehicle clearly improves the cytotoxic effectiveness of metal-based drugs against cancer cells. One of the most potent between all tested systems is material SBA-15~Cl|Ph3Sn(CH2)8OH. Its cytotoxicity seems to come from additional mechanisms apart from apoptosis provoking cell reprogram in B16 melanoma into more mature and less aggressive phenotype. Moderated production of ROS/RNS is probably in the background of observed phenomenon. Obtained results are further confirmed in syngeneic mouse model of melanoma in C57BL6 mice. The in vivo results show that SBA-15 do not disturb tumor growth, while both Ph3Sn(CH2)8OH and SBA-15~Cl|Ph3Sn(CH2)8OH significantly decreases tumor volume with an enhancement of the antitumor potential of the tetraorganotin(IV) compound upon immobilization in SBA-15.