Patel Kunal, Sundara Raj Behin, Chen Yan, Lou Xia
Department of Chemical Engineering, Curtin University, Kent Street, Bentley, WA 6102, Australia.
School of Pharmacy, CHIRI-Biosciences, Curtin University, Kent Street, Bentley, WA 6102, Australia.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:213-222. doi: 10.1016/j.colsurfb.2015.12.046. Epub 2015 Dec 29.
Hollow silica nanoparticles of two sizes with and without a folic acid targeting ligand were synthesized. Fickian diffusion of the antitumor drug doxorubicin hydrochloride (DOX) was demonstrated by the produced nanoparticles, achieving a cumulative release of 73% and 45% for 215 nm and 430 nm particles respectively over a period of 500 h. The hollow silica nanoparticles presented a time and dose dependent toxicity, selective to human epithelial colorectal adenocarcinoma (Caco2) cells, over mouse embryonic fibroblast (3T3) cells. At 24h Caco2 cell viability was reduced to 66% using pure hollow silica at a concentration of 50 μg mL(-1), while that of 3T3 cells remained at 94% under the same conditions. The selective cytotoxicity of hollow silica nanoparticles was further enhanced by conjugation of folic acid and incorporation of DOX: at 24h and an equivalent DOX concentration of 0.5 μg mL(-1), viable Caco2 cells were reduced to 45% while 3T3 cells were reduced to 83%. Interestingly the equivalent dose of free DOX was more toxic to 3T3 than to Caco2 cells, reducing the 3T3 viability to 72% and the Caco2 viability to 80%, which is likely due to the presence of the p-glycoprotein pumps in Caco2 cells. Folic acid conjugation served to enhance the viability of both cell lines in this work. Careful optimization of the folate content should further improve the cell specificity of the hollow silica nanoparticles, thus providing a viable targeting platform for cancer therapy.
合成了两种尺寸的带有和不带有叶酸靶向配体的中空二氧化硅纳米颗粒。所制备的纳米颗粒证明了抗肿瘤药物盐酸阿霉素（DOX）的菲克扩散，在500小时内，215纳米和430纳米颗粒的累积释放率分别达到73%和45%。中空二氧化硅纳米颗粒呈现出时间和剂量依赖性毒性，对人上皮结直肠癌（Caco2）细胞具有选择性，而对小鼠胚胎成纤维细胞（3T3）细胞则不然。在24小时时，使用浓度为50μg mL(-1)的纯中空二氧化硅，Caco2细胞活力降至66%，而在相同条件下3T3细胞活力仍保持在94%。通过叶酸偶联和DOX掺入进一步增强了中空二氧化硅纳米颗粒的选择性细胞毒性：在24小时且DOX等效浓度为0.5μg mL(-1)时，存活的Caco2细胞降至45%，而3T3细胞降至83%。有趣的是，游离DOX的等效剂量对3T3细胞的毒性比对Caco2细胞更大，使3T3细胞活力降至72%，Caco2细胞活力降至80%，这可能是由于Caco2细胞中存在P-糖蛋白泵。在这项研究中，叶酸偶联有助于提高两种细胞系的活力。仔细优化叶酸含量应能进一步提高中空二氧化硅纳米颗粒的细胞特异性，从而为癌症治疗提供一个可行的靶向平台。
