Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
Int J Nanomedicine. 2021 Apr 22;16:2995-3020. doi: 10.2147/IJN.S302238. eCollection 2021.
In chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract's hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells.
fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29.
fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and -1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such.
In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.
在化疗中，由于缺乏对局部结肠癌细胞的药物特异性，口服给药受到限制。药物无法区分癌细胞和正常细胞，会产生副作用。聚合物纳米颗粒药物递送的结肠靶向提供了将疏水性药物递送到靶部位的高潜力策略，并且副作用更少。由于其在还原条件下结肠降解的潜力以及抵抗上胃肠道恶劣环境的能力，最近二硫键交联聚合物获得了高度重视。因此，本项目的目的是开发 pH 敏感和氧化还原响应的荧光素标记的麦胚凝集素（fWGA）负载的二硫键交联海藻酸钠纳米粒子（fDTP2），直接靶向结肠癌细胞中的多西紫杉醇（DTX）。
通过两步碳化二亚胺法将 fWGA 固定在载有 DTX 的纳米粒子（DTP2）上制备 fDTP2。使用扫描电子显微镜（SEM）和透射电子显微镜（TEM）观察 fDTP2 的形态。动态光散射（DLS）研究用于确定 fDTP2 的平均直径、多分散指数（PDI）和 zeta 电位。使用荧光微孔板读数仪测定细胞摄取效率。在 HT-29 上进行 fDTP2 的生物相容性和主动内化。
fDTP2 的 DTX 负载效率为 19.3%。SEM 和 TEM 测试显示出球形纳米粒子。体外 DTX 释放试验显示累积释放 54.7%。从 DLS 研究中，fDTP2 报告的平均直径为 277.7nm，PDI 低于 0.35，zeta 电位为-1.0mV。与 L929 相比，用 fDTP2 处理的 HT-29 显示出较低的活力，半数最大抑制浓度（IC）为 34.7μg/mL。在 2 小时孵育时，HT-29 高效摄取 fDTP2（33.4%）。通过荧光和共聚焦成像研究表明，HT-29 对纳米颗粒的主动内化。
总之，fDTP2 作为结肠药物递送 DTX 载体具有潜力。
