Kumar Pramod, Tambe Prajakta, Paknikar Kishore M, Gajbhiye Virendra
Nanobioscience Group, Agharkar Research Institute, Pune 411 004, India; Savitribai Phule Pune University, Ganeshkhind, Pune 411 007, India.
Nanobioscience Group, Agharkar Research Institute, Pune 411 004, India; Savitribai Phule Pune University, Ganeshkhind, Pune 411 007, India.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:203-212. doi: 10.1016/j.colsurfb.2017.05.032. Epub 2017 May 11.
Folate receptors (FR) have been well recognized as a marker to target nano-sized carriers for cancer diagnosis and therapy. In contrast, influx transport systems (e.g. GLUT transporters) that transport essential amino acids and nutrients to cancer cells have not been exploited much for targeted delivery. In this study, folic acid- or n-acetyl glucosamine- functionalized mesoporous silica nanoparticles loaded with doxorubicin (DOX-FA-MSNPs or DOX-NAG-MSNPs) were prepared, characterized and compared for targeting along with cytotoxicity towards MCF-7 and MDA-MB-231 human breast cancer cells. Cellular uptake of FITC tagged FA-MSNPs and NAG-MSNPs were evaluated by confocal microscopy and flow cytometry in above-mentioned cancer cell lines. The result suggested higher cellular uptake of NAG-MSNPs than FA-MSNPs for both the cell lines. Cytotoxicity of free DOX, DOX-MSNPs, DOX-FA-MSNPs and DOX-NAG-MSNPs were evaluated on both the breast cancer cell lines. Cytotoxicity results showed that DOX-loaded NAG-MSNPs exerted significant higher cytotoxicity effect on both the cell lines than DOX-FA-MSNPs. Moreover, both the targeted formulations were more effective than free DOX. Our results suggested that GLUT transporters can be effectively utilized for nanoparticles internalization in breast cancer cells.
叶酸受体(FR)已被公认为是用于癌症诊断和治疗的纳米级载体的靶向标记物。相比之下,将必需氨基酸和营养物质转运至癌细胞的内流运输系统(如葡萄糖转运蛋白)在靶向递送方面尚未得到充分利用。在本研究中,制备了负载阿霉素的叶酸或N-乙酰葡糖胺功能化介孔二氧化硅纳米颗粒(DOX-FA-MSNPs或DOX-NAG-MSNPs),对其进行了表征和比较,并研究了它们对MCF-7和MDA-MB-231人乳腺癌细胞的靶向性及细胞毒性。通过共聚焦显微镜和流式细胞术评估了上述癌细胞系中FITC标记的FA-MSNPs和NAG-MSNPs的细胞摄取情况。结果表明,两种细胞系中NAG-MSNPs的细胞摄取量均高于FA-MSNPs。评估了游离阿霉素、DOX-MSNPs、DOX-FA-MSNPs和DOX-NAG-MSNPs对两种乳腺癌细胞系的细胞毒性。细胞毒性结果显示,负载阿霉素的NAG-MSNPs对两种细胞系的细胞毒性作用均显著高于DOX-FA-MSNPs。此外,两种靶向制剂均比游离阿霉素更有效。我们的结果表明,葡萄糖转运蛋白可有效用于纳米颗粒在乳腺癌细胞中的内化。