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Exploration of RGD peptide-modified targeted delivery of doxorubicin using chitosan oligosaccharide-coated GQD
Tseng-Yu Yeh1, Jung-Hua Lin1, Yi-Jhen Jiang2
1Department of Science Education, National Taipei University of Education, No.134, Sec. 2, Heping E. Rd., Da-an District, Taipei City 106, Taiwan.
Abstract:
Cancer therapy is often limited by suboptimal tumor targeting and systemic toxicity. To address these challenges, a pre-modified drug with targeting ligands, such as the RGD-4C peptide, has emerged as a potential strategy. However, pre-modified doxorubicin (RGD-DOX) alters traditional interactions among the drug, delivery systems, and cancer cells. In this study, we investigated two graphene quantum dot (GQD)-based carriers with distinct complexities for delivering RGD-DOX. The first carrier, PEGylated GQDs with gold nanoparticles (APG), leveraged enhanced colloidal stability and multifunctionality, while the second, a chitosan oligosaccharide-coated GQD (CG), offered charge-based encapsulation and biodegradability. Both carriers effectively encapsulated RGD-modified DOX, demonstrating pH-responsive drug release triggered by the acidic tumor microenvironment. In vitro studies revealed that RGD-DOX delivered by both carriers induced significant cellular apoptosis through mechanisms similar to unmodified DOX, as evidenced by DNA damage and apoptotic markers. In vivo experiments further verified effective tumor suppression with less loaded DOX medicine, which could minimize systemic toxicity. These findings validate the potential of an RGD-pre-modified DOX based on one step assembly-GQD drug delivery systems, demonstrating high targeting efficiency with reduced potential side effects, and presenting a novel strategy for drug delivery system design.
Insights
This study explores graphene quantum dot (GQD) carriers for delivering RGD-modified doxorubicin (RGD-DOX) in cancer therapy. These novel drug delivery systems show high tumor targeting efficiency and reduced side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Cancer therapy faces challenges with tumor targeting and systemic toxicity.
- Pre-modified drugs with targeting ligands, like RGD-4C peptide, offer a potential solution.
- RGD-modified doxorubicin (RGD-DOX) presents unique interactions with delivery systems and cancer cells.
Purpose of the Study:
- To investigate two distinct graphene quantum dot (GQD)-based carriers for delivering RGD-DOX.
- To evaluate the efficacy and safety of these novel drug delivery systems in cancer treatment.
Main Methods:
- Two GQD carriers were developed: PEGylated GQDs with gold nanoparticles (APG) and chitosan oligosaccharide-coated GQD (CG).
- Both carriers encapsulated RGD-DOX and demonstrated pH-responsive release in acidic tumor environments.
- In vitro and in vivo studies assessed cellular apoptosis, tumor suppression, and systemic toxicity.
Main Results:
- Both APG and CG carriers effectively delivered RGD-DOX, inducing significant cellular apoptosis via DNA damage and apoptotic markers.
- In vivo experiments showed effective tumor suppression with reduced RGD-DOX dosage, indicating minimized systemic toxicity.
- The RGD-pre-modified DOX delivered by GQD systems demonstrated high targeting efficiency.
Conclusions:
- GQD-based drug delivery systems are validated as a novel strategy for RGD-pre-modified doxorubicin.
- These systems offer high targeting efficiency and reduced potential side effects in cancer therapy.
- The study presents a promising approach for designing advanced drug delivery systems.
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