Mekuria Shewaye Lakew, Debele Tilahun Ayane, Chou Hsiao-Ying, Tsai Hsieh-Chih
Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology , Taipei 106, Taiwan ROC.
J Phys Chem B. 2016 Jan 14;120(1):123-30. doi: 10.1021/acs.jpcb.5b11125. Epub 2015 Dec 24.
In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5-RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells.
在本研究中,聚酰胺 - 胺(PAMAM)树枝状大分子(G4.5)与两种靶向部分,即白细胞介素 - 6(IL - 6)抗体和RGD肽(G4.5 - IL6和G4.5 - RGD缀合物)缀合。将阿霉素抗癌药物物理负载到G4.5 - IL6和G4.5 - RGD上,包封效率分别为51.3%和30.1%。分别使用HeLa细胞,通过共聚焦显微镜和流式细胞术观察并比较了G4.5 - IL6/阿霉素和G4.5 - RGD/阿霉素复合物的细胞内化和摄取效率。与G4.5 - RGD/阿霉素相比,G4.5 - IL6/阿霉素的半数抑制浓度(IC50)值较低,这表明更高的药物负载量和更快的药物释放速率与更大的细胞毒性相对应。由于通过受体介导的内吞作用递送药物,晚期凋亡/坏死细胞增加,进一步证实了细胞毒性作用。基于这些结果,G4.5 - IL6是一种更适合将阿霉素靶向递送至宫颈癌细胞的载体。