Norouzi Parisa, Amini Mohsen, Mottaghitalab Fatemeh, Mirzazadeh Tekie Farnaz Sadat, Dinarvand Rassoul, Mirzaie Zahra Hadavand, Atyabi Fatemeh
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Chem Biol Drug Des. 2020 Aug;96(2):745-757. doi: 10.1111/cbdd.13044. Epub 2020 Apr 26.
Dual-targeted drug delivery system has established their reputation as potent vehicles for cancer chemotherapies. Herein, gemcitabine (Gem) was conjugated to human serum albumin (HSA) via dithiodipropionic anhydride to fabricate Gem-HSA nanoparticles. It was hypothesized that this system can enhance the low stability of Gem and can improve its intracellular delivery. Furthermore, folate was applied as targeting agent on HSA nanoparticles for increasing the tumor selectivity of Gem. To evaluate the structural properties of synthesized products, H NMR and FT-IR were performed. Moreover, HPLC was implemented for confirming the conjugation between HSA and Gem. Nanoparticles have shown spherical shape with negative charge. The release rate of Gem was dependent to the concentration of glutathione and pH. Folate-targeted HSA nanoparticles have shown higher cytotoxicity, cellular uptake, and apoptosis induction on folate receptor overexpressing MDA-MB-231 cells in comparison to non-targeted nanoparticles. Finally, it is considered that the developed dual-targeted nanoparticles would be potent in improving the stability and efficacy of intracellular delivery of Gem and its selective delivery to cancer cells.
双靶向给药系统已成为癌症化疗的有效载体而声名远扬。在此，吉西他滨（Gem）通过二硫代二丙酸酐与人血清白蛋白（HSA）偶联，制备Gem-HSA纳米颗粒。据推测，该系统可增强Gem的低稳定性，并改善其细胞内递送。此外，叶酸被用作HSA纳米颗粒上的靶向剂，以提高Gem的肿瘤选择性。为评估合成产物的结构性质，进行了1H NMR和FT-IR分析。此外，采用HPLC确认HSA与Gem之间的偶联。纳米颗粒呈球形且带负电荷。Gem的释放速率取决于谷胱甘肽浓度和pH值。与非靶向纳米颗粒相比，叶酸靶向的HSA纳米颗粒对叶酸受体过表达的MDA-MB-231细胞表现出更高的细胞毒性、细胞摄取和凋亡诱导作用。最后，认为所开发的双靶向纳米颗粒在提高Gem细胞内递送的稳定性和功效及其向癌细胞的选择性递送方面将具有强大作用。
