Marshall Suphalak Khamruang, Panrak Yada, Makchuchit Naritsara, Jaroenpakdee Passara, Saelim Boonyisa, Taweesap Maneerat, Pachana Verachai
Department of Radiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Bioengineering (Basel). 2022 Jun 30;9(7):294. doi: 10.3390/bioengineering9070294.
Currently, breast-cancer treatment has a number of adverse side effects and is associated with poor rates of progression-free survival. Therefore, a radiolabeled anti-EpCAM targeted biomimetic coated nanocarrier (EINP) was developed in this study to overcome some of the treatment challenges. The double emulsion method synthesized the poly(lactic-co-glycolic acid) (PLGA) nanoparticle with Na131I entrapped in the core. The PLGA nanoparticle was coated in human red blood cell membranes and labeled with epithelial cell adhesion molecule (EpCAM) antibody to enable it to target EpCAM overexpression by breast-cancer cells. Characterization determined the EINP size as 295 nm, zeta potential as −35.9 mV, and polydispersity as 0.297. EINP radiochemical purity was >95%. Results determined the EINP efficacy against EpCAM positive MCF-7 breast cancer at 24, 48, and 72 h were 69.11%, 77.84%, and 74.6%, respectively, demonstrating that the EINPs achieved greater cytotoxic efficacy supported by NIS-mediated Na131I uptake than the non-targeted 131INPs and Na131I. In comparison, fibroblast (EpCAM negative) treated with EINPs had significantly lower cytotoxicity than Na131I and 131INPs (p < 0.05). Flow cytometry fluorescence imaging visually signified delivery by EINPs specifically to breast-cancer cells as a result of anti-EpCAM targeting. Additionally, the EINP had a favorable safety profile, as determined by hemolysis.
目前，乳腺癌治疗存在许多不良副作用，且无进展生存率较低。因此，本研究开发了一种放射性标记的抗上皮细胞黏附分子（EpCAM）靶向仿生包被纳米载体（EINP），以克服一些治疗挑战。采用双乳液法合成了核内包裹Na131I的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒。PLGA纳米颗粒用人类红细胞膜包被，并用上皮细胞黏附分子（EpCAM）抗体标记，使其能够靶向乳腺癌细胞中过表达的EpCAM。表征结果显示EINP的尺寸为295 nm，zeta电位为−35.9 mV，多分散性为0.297。EINP的放射化学纯度>95%。结果表明，EINP在24、48和72小时对EpCAM阳性MCF-7乳腺癌的疗效分别为69.11%、77.84%和74.6%，表明与非靶向的131INP和Na131I相比，EINP通过NIS介导的Na131I摄取实现了更高的细胞毒性疗效。相比之下，用EINP处理的成纤维细胞（EpCAM阴性）的细胞毒性明显低于Na131I和131INP（p<0.05）。流式细胞术荧光成像直观地显示，由于抗EpCAM靶向作用，EINP特异性地将药物递送至乳腺癌细胞。此外，溶血试验表明EINP具有良好的安全性。
