Design, Preparation, and Characterization of L-Glutamic Acid Functionalized Graphene Oxide (GO-L-Glu) for Application in Targeted Cancer Therapy
نویسندگان
1 Department of Pharmacy, College of Pharmacy, Al-Nisour University, Baghdad, Iraq
2 Al-Hadi University College, Baghdad, Iraq
3 INTI International University, 71800 Negeri Sembilan, Malaysia
4 Department of Orthopedic Dentistry and Orthodontics, Bukhara State Medical Institute, Bukhara, Uzbekistan
5 Department of Orthopedic Dentistry and Orthodontics, Bukhara State Medical Institute, Bukhara, Uzbekistan
6 Axmadulina Galiya - Department of Therapeutic Sciences, Fergana Medical Institute of Public Health, Fergana, Uzbekistan
7 Department of Infectious Diseases, Andijan State Medical Institute, Andijan, Uzbekistan
8 Faculty of Business and Communications, INTI International University, 71800 Negeri Sembilan, Malaysia.
9 Department of Pharmaceutics, College of Pharmacy, University of Al-Ameed, Iraq
10 Department of Pharmacy, Al-Turath University, Baghdad, Iraq
11 College of Health and Medical Technologies, National University of Science and Technology, Dhi Qar, Iraq
12 Department of General Surgery, Samarkand State Medical University, Samarkand 140100, Uzbekistan
13 Department of Therapeutic Sciences, Fergana Medical Institute of Public Health, Fergana, Uzbekistan
14 Department of Fashion Design, Tashkent Institute of Textile and Light Industry, Uzbekistan
doi
10.22052/JNS.2026.02.034چکیده
The development of targeted nanocarriers that selectively deliver chemotherapeutic agents to tumor cells remains a critical challenge in oncology. This study reports the rational design, synthesis, and comprehensive characterization of a novel nanoplatform based on L-glutamic acid-functionalized graphene oxide (GO-L-Glu) for targeted cancer therapy. The covalent conjugation was achieved via a carbodiimide-mediated amidation reaction, meticulously optimized to ensure high functionalization density. Advanced characterization techniques, including FT-IR and TGA, confirmed successful grafting, with TGA indicating a substantial increase in organic content. The GO-L-Glu carrier demonstrated a high loading capacity (45.7%) for doxorubicin (DOX) and exhibited a pronounced pH-responsive release profile, with 88.7% of DOX released at pH 5.0 versus only 42.5% at pH 7.4 over 72 hours. In vitro studies revealed that the GO-L-Glu/DOX conjugate maintained potent cytotoxicity against xCT transporter-overexpressing cancer cell lines (MDA-MB-231 and U-87 MG) while showing significantly reduced toxicity towards normal human dermal fibroblasts. A competitive inhibition assay using sulfasalazine mechanistically proved that cellular uptake occurs primarily via xCT-mediated endocytosis. Furthermore, functionalization drastically improved hemocompatibility, reducing hemolysis by more than 50% compared to pristine GO. These collective results validate GO-L-Glu as a multifunctional, safe, and highly selective nanocarrier, offering a promising strategy for targeting tumor metabolism and overcoming limitations of conventional chemotherapy.
