The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
ChemMedChem. 2021 Jan 8;16(1):108-112. doi: 10.1002/cmdc.202000384. Epub 2020 Jul 30.
Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a Ti -based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.
口服抗癌药物便于治疗，但胃部的酸性环境常常影响其有效性。PhenolaTi 是一种基于钛的无毒抗癌药物，具有显著的体内疗效。我们报告说，纳米制剂可保护 PhenolaTi 免受类似胃部条件下的分解。这一点可以通过在 pH 值 2 下孵育纳米制剂 PhenolaTi（PhenolaTi-F）前后，核磁特征相似和对小鼠（CT-26）和人（HT-29）结肠癌细胞的体外细胞毒性相似来证明，而未经制剂处理的复合物则没有这样的结果。此外，在分别接种 CT-26 和 HT-29 细胞的 Balb/c 和免疫缺陷（裸）小鼠的饮用水中给予 PhenolaTi-F，可显著抑制肿瘤生长。体内疗效至少与 PhenolaTi-F 的相应腹腔内治疗和临床上使用的口服药物卡培他滨相当。在接受 PhenolaTi-F 治疗的动物中，没有体重减轻或明显的毒性临床症状。这些发现证明了通过安全的基于钛的药物口服给药的一种新的便捷癌症治疗模式。
