Tiash Snigdha, Othman Iekhsan, Rosli Rosita, Chowdhury Ezharul Hoque
Jeffrey Cheah School of Medicine and Health Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Malaysia.
Curr Drug Deliv. 2014;11(2):214-22. doi: 10.2174/1567201810666131211101819.
Most of the classical drugs used today to destroy cancer cells lead to the development of acquired resistance in those cells by limiting cellular entry of the drugs or exporting them out by efflux pumps. As a result, higher doses of drugs are usually required to kill the cancer cells affecting normal cells and causing numerous side effects. Accumulation of the therapeutic level of drugs inside the cancer cells is thus required for an adequate period of time to get drugs' complete therapeutic efficacy minimizing the side effects on normal cells. In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in this study to make complexes with three classical anticancer drugs, methotrexate, cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to apatite were evaluated by absorbance and HPLC analysis and the therapeutic efficacy of drug-apatite complexes was determined by cell viability assay. Carbonate apatite demonstrated significant binding affinity towards methotrexate and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7 and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite with resulting tiny particles less than 100 nm in diameter further promoted binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted apatite nanoparticles have the high potential for loading substantial amount of anti-cancer drugs with eventual more therapeutic effectiveness.
如今用于摧毁癌细胞的大多数传统药物会通过限制药物进入细胞或借助外排泵将药物排出细胞，从而导致这些细胞产生获得性耐药性。结果，通常需要更高剂量的药物来杀死癌细胞，这会影响正常细胞并引发众多副作用。因此，需要在癌细胞内足够长的时间内积累达到治疗水平的药物，以获得药物的完全治疗效果，同时将对正常细胞的副作用降至最低。为了提高化疗药物的疗效，本研究使用了碳酸磷灰石纳米颗粒及其锶（Sr(2+)）取代衍生物与三种传统抗癌药物甲氨蝶呤、环磷酰胺和5-氟尿嘧啶形成复合物。通过吸光度和高效液相色谱分析评估了这些药物与磷灰石的结合亲和力，并通过细胞活力测定确定了药物-磷灰石复合物的治疗效果。碳酸磷灰石对甲氨蝶呤和环磷酰胺表现出显著的结合亲和力，在MCF-7和4T1乳腺癌细胞中比游离药物导致更多的细胞毒性。此外，碳酸磷灰石中的Sr(2+)取代产生了直径小于100nm的微小颗粒，进一步促进了甲氨蝶呤与纳米载体的结合，表明Sr(2+)取代的磷灰石纳米颗粒具有装载大量抗癌药物的高潜力，最终具有更高的治疗效果。
