Fabrication and Characterization of an Engineered Graphene Oxide Quantum Dot-Polyethyleneimine-Hyaluronic Acid Nanocarrier: A Safe and Potentially Targetable Platform for Future Gene Therapy
| Author | Zahra Samadi | en |
| Author | Roshanak Yadegarazari | en |
| Author | Mina Habibizadeh | en |
| Author | Nasser Nikfarjam | en |
| Author | Soheila Mohammadi | en |
| Author | Omid Tavallaei | en |
| Orcid | Zahra Samadi [0009-0001-4139-8348] | en |
| Orcid | Mina Habibizadeh [0000-0002-8340-8807] | en |
| Orcid | Soheila Mohammadi [0000-0001-8779-6440] | en |
| Orcid | Omid Tavallaei [0000-0001-5268-3016] | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: The global rise in cancer incidence underscores the urgent need for novel and more effective therapeutic strategies. Among emerging modalities, gene therapy offers a powerful and precise approach by directly modulating genetic pathways involved in tumor growth. However, the success of gene therapy depends critically on the development of safe, efficient, and target-specific carriers capable of condensing, protecting, and delivering nucleic acids to cancer cells with minimal toxicity. Objectives: This study aimed to develop and characterize a novel, biocompatible nanocarrier system based on graphene oxide quantum dots (GOQDs) functionalized with polyethylenimine (PEI) and hyaluronic acid (HA) for potential CD44-targeted gene delivery applications. Methods: The GOQD/PEI/HA nanocarrier was synthesized by covalent conjugation using EDC/NHS chemistry and characterized by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA), which confirmed successful functionalization. DNA-binding and condensation were assessed by agarose gel retardation, and field-emission scanning electron microscopy (FE-SEM) was used to determine the size and surface morphology of the prepared complexes. Finally, hemocompatibility and cytocompatibility were evaluated using hemolysis test and MTT assay in HeLa cells. Results: TGA and FT-IR analyses confirmed the successful preparation of functionalized GOQD/PEI/HA NPs. The gel retardation assay demonstrated complete plasmid DNA (pDNA) condensation at a 1:2 pDNA-to-carrier ratio, confirming a strong electrostatic interaction between the DNA and the carrier. Hemolysis rates remained below 2% at all tested concentrations, demonstrating the high hemocompatibility of the carriers. Moreover, MTT assay results showed that HA conjugation significantly increased cell viability from approximately 76% for GOQD/PEI to above 90% for GOQD/PEI/HA, indicating a substantial reduction in GOQD/PEI-associated cytotoxicity. Conclusions: Collectively, these findings confirm that the covalently HA-modified GOQD/PEI nanocarrier effectively integrates strong gene-condensation capability with excellent biocompatibility and hemocompatibility. This system represents a promising and safe nonviral platform with the potential for targeted gene delivery to CD44-positive HeLa cancer cells. Future studies should assess its therapeutic efficacy in more physiologically relevant models, including 3D tumor spheroids, organoid cultures, and in vivo systems, to validate its potential for advanced cancer gene therapy applications. | en |
| DOI | https://doi.org/10.5812/jrps-168444 | en |
| URI | https://brieflands.com/journals/jrps/articles/168444 | en |
| Keyword | Gene Delivery | en |
| Keyword | Graphene Oxide Quantum Dots | en |
| Keyword | Polyethylenimine | en |
| Keyword | Hyaluronic Acid | en |
| Keyword | Cancer | en |
| Publisher | Brieflands | en |
| Title | Fabrication and Characterization of an Engineered Graphene Oxide Quantum Dot-Polyethyleneimine-Hyaluronic Acid Nanocarrier: A Safe and Potentially Targetable Platform for Future Gene Therapy | en |
| Type | Research Article | en |