Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, PR China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250022, PR China.
Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, PR China.
Int J Pharm. 2015 Dec 30;496(2):1026-33. doi: 10.1016/j.ijpharm.2015.10.080. Epub 2015 Nov 2.
In order to enhance the therapeutic efficacy and intracellular concentration of bevacizumab (BVC), we have designed a novel tumor endothelial marker 1 (TEM1)/endosialin (Ab-/scFv)-conjugated mesoporous silica nanoparticles (MSN) to target ovarian cancer cell. The Ab-/scFv-conjugated MSN were prepared by the conjugation of amine functional group of antibody of the carboxyl group of MSN. The resultant MSN was nanosized, spherical shaped, and exhibited a controlled release phenomenon in pH 7.4 conditions. Furthermore, BMSN/Ab was found to increase the cellular uptake and intracellular distribution of BVC in OVCAR-5 cancer cells. The Ab- conjugated MSN exhibited a superior anticancer effect with profound apoptosis in cancer cells in a time- and concentration dependent manner. Consistently, BMSN/Ab effectively inhibited the colony formation in transwell plate. Finally, BMSN/Ab showed a notable increase in the proportion of cells in G2/M phase of cell cycle indicating promising anticancer efficacy profile. Overall, Ab-/scFv-conjugated MSN might provide an effective strategy for the therapeutic management of ovarian cancers.
为了提高贝伐单抗（BVC）的治疗效果和细胞内浓度，我们设计了一种新型的肿瘤内皮标志物 1（TEM1）/内唾液酸酶（Ab-/scFv）-偶联介孔硅纳米粒子（MSN）来靶向卵巢癌细胞。Ab-/scFv 偶联的 MSN 是通过抗体的氨基与 MSN 的羧基偶联制备的。所得的 MSN 呈纳米级、球形，并在 pH7.4 条件下表现出控制释放现象。此外，BMSN/Ab 被发现增加了 OVCAR-5 癌细胞中 BVC 的细胞摄取和细胞内分布。Ab 偶联的 MSN 表现出优越的抗癌效果，在时间和浓度依赖性方式下，诱导癌细胞发生深刻的凋亡。一致地，BMSN/Ab 有效地抑制了 Transwell 板中的集落形成。最后，BMSN/Ab 使细胞周期 G2/M 期的细胞比例显著增加，表明具有有前景的抗癌功效特征。总体而言，Ab-/scFv 偶联的 MSN 可能为卵巢癌的治疗管理提供一种有效的策略。
