Department of Pharmacy, Shanghai Ninth People\'s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Curr Pharm Biotechnol. 2022;23(6):835-846. doi: 10.2174/1389201022666210719164538.
The purpose of this research is to formulate a biomimetic drug delivery system, which can selectively target glioblastoma (GBM) to deliver the antitumor agent, Gboxin, a novel Complex V inhibitor. Gboxin can specifically inhibit GBM cell growth but not normal cells.
In the present study, we utilized red blood cell (RBC) membrane and U251 cell membrane to obtain a hybrid biomimetic membrane (RBC-U), and prepared RBC-U coated Gboxin-loaded mesoporous silica nanoparticles ((MSNs/Gboxin)@[RBC-U]) for GBM chemotherapy. The zeta potential, particle size, and morphology of (MSNs/Gboxin)@[RBC-U] were characterized. The cellular uptake, effect of cells growth inhibition, biocompatibility, and specific self-recognition of nanoparticles were evaluated.
The (MSNs/Gboxin)@[RBC-U] was successfully fabricated and possessed high stability in the circulation system. The drug loading of Gboxin was 13.9%. (MSNs/Gboxin)@ [RBC-U] could effectively retain drugs in the physiological environment and released Gboxin rapidly in the tumor cells. Compared to the MSNs/Gboxin, the (MSNs/Gboxin)@[RBC-U] exhibit highly specific self-recognition to the source cell line. Additionally, the (MSNs/Gboxin) @[RBC-U] showed excellent anti-proliferation efficiency (IC50 = 0.21 μg/mL) in the tumor cell model and few side effects in normal cels in vitro.
The (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effects in vitro and the specific self-recognition to GBM cells. Hence, (MSNs/Gboxin)@[RBC-U] could be a promising delivery system for GBM targeted therapy.
本研究旨在构建一种仿生药物递送系统,该系统能够选择性地靶向神经胶质瘤(GBM),递输送氧复合物 V 抑制剂 Gboxin。Gboxin 可以特异性地抑制 GBM 细胞生长,而对正常细胞无影响。
本研究利用红细胞(RBC)膜和 U251 细胞膜制备杂交仿生膜(RBC-U),并制备 RBC-U 包裹的载 Gboxin 的介孔硅纳米粒子((MSNs/Gboxin)@[RBC-U])用于 GBM 化疗。对(MSNs/Gboxin)@[RBC-U]的表面zeta 电位、粒径和形态进行了表征。评估了细胞摄取、细胞生长抑制效果、生物相容性和纳米粒子的特异性自识别。
成功制备了(MSNs/Gboxin)@[RBC-U],其在循环系统中具有高稳定性。Gboxin 的载药量为 13.9%。(MSNs/Gboxin)@[RBC-U]能够在生理环境中有效保留药物,并在肿瘤细胞中快速释放 Gboxin。与 MSNs/Gboxin 相比,(MSNs/Gboxin)@[RBC-U]对来源细胞系具有高度特异性的自识别。此外,(MSNs/Gboxin)@[RBC-U]在肿瘤细胞模型中表现出优异的抗增殖效率(IC50=0.21μg/mL),在体外对正常细胞几乎没有副作用。
(MSNs/Gboxin)@[RBC-U]在体外具有显著的抗癌作用和对 GBM 细胞的特异性自识别。因此,(MSNs/Gboxin)@[RBC-U]可能成为一种有前途的 GBM 靶向治疗递送系统。