Meker Sigalit, Margulis-Goshen Katrin, Weiss Ester, Braitbard Ori, Hochman Jacob, Magdassi Shlomo, Tshuva Edit Y
The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel).
ChemMedChem. 2014 Jun;9(6):1294-8. doi: 10.1002/cmdc.201400038. Epub 2014 Mar 26.
Nanoparticles of titanium(IV) complexes of phenolato ligands were formed and evaluated for cytotoxicity toward human HT-29 colon cancer, murine T-25 lymphoma, and murine HU-2 multidrug-resistant (MDR) cells. The nano-formulation, besides increasing the complexes' shelf lives, is particularly efficient in overcoming limitations in solubility and cell-penetration, thus enhancing biological accessibility; large complexes that were inactive when measured in a non-formulated form showed marked activity when nano-formulated. For active and accessible small complexes, the effect of the formulation was negligible. Most complexes showed similar activity toward MDR cells and their drug-sensitive analogues, further increasing their therapeutic potential. An exception is a particularly hydrophobic complex, which is presumably more accessible to interaction with the membrane ABCB1 (MDR1) transporter active in the multidrug resistance of HU-2 cells. The most efficient compound is a mononuclear complex of a single hexadentate ligand, combining particularly high activity and hydrolytic stability with accessibility aided by the nano-formulation.
形成了酚盐配体的钛（IV）配合物纳米颗粒，并评估了其对人HT-29结肠癌细胞、鼠T-25淋巴瘤细胞和鼠HU-2多药耐药（MDR）细胞的细胞毒性。这种纳米制剂除了能延长配合物的保质期外，在克服溶解性和细胞穿透性方面的局限性特别有效，从而提高了生物可及性；以非制剂形式测量时无活性的大配合物，在制成纳米制剂后显示出显著活性。对于活性且可及的小配合物，制剂的影响可忽略不计。大多数配合物对MDR细胞及其药物敏感类似物表现出相似的活性，进一步提高了它们的治疗潜力。一个例外是一种特别疏水的配合物，据推测它更容易与在HU-2细胞多药耐药中起作用的膜ABCB1（MDR1）转运蛋白相互作用。最有效的化合物是一种单六齿配体的单核配合物，它结合了特别高的活性和水解稳定性以及纳米制剂辅助的可及性。
