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Fine-Tuning Positive-Surface-Charge Carbon Dots for High-Efficiency and Low-Cytotoxicity Gene Delivery
Shuo Zhang1, Yangming Zhou1, Qi Zhang1
1Shanxi Key Laboratory of Artificial Intelligence & Micro Nano Sensors, School of Integrated Circuit, Taiyuan University of Technology, Taiyuan 030024, China.
Nanomaterials (Basel, Switzerland)
|February 12, 2026
Summary
Positive-charged carbon dots (CDs) show promise as safe, efficient gene delivery vectors for osteoarthritis therapy. Optimized CDs-3 demonstrated superior transfection and regulation of key pathways in chondrocytes compared to commercial options.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- Carbon dots (CDs) are emerging as biocompatible, non-viral gene delivery vectors.
- Their tunable surface properties, particularly zeta potential, are crucial for effective gene delivery.
- Osteoarthritis (OA) poses a significant health burden, necessitating advanced therapeutic strategies.
Purpose of the Study:
- To synthesize and characterize carbon dots (CDs) with varying positive zeta potentials for gene delivery.
- To evaluate the efficacy and safety of an optimized CD-based system for delivering small interfering RNA targeting the Indian Hedgehog (Ihh) pathway in chondrocytes.
- To assess the potential of this novel vector for osteoarthritis gene therapy.
Main Methods:
- Hydrothermal synthesis of four CDs with gradient-positive zeta potentials.
- Characterization of CDs' cytotoxicity and transfection efficiency using GFP plasmid delivery.
- Construction and in vitro evaluation of a CDs-3/siIhh delivery system in normal and IL-1β-induced ATDC5 chondrocytes.
- Assessment of the regulation of the Indian Hedgehog (Ihh) signaling pathway and OA-related markers.
Main Results:
- CDs with zeta potentials ranging from 7.23 mV to 34.5 mV were successfully synthesized.
- CDs-3 (25.3 mV) exhibited ultra-low cytotoxicity (>80% viability at 50 μg/mL) and nearly 100% transfection efficiency for GFP plasmid.
- The CDs-3/siIhh system demonstrated superior regulation of the Ihh pathway and OA markers in chondrocytes compared to Lipo2000/siIhh and PEI/siIhh.
- Efficient cellular internalization of CDs-3 in chondrocytes was observed.
Conclusions:
- Optimized positive-charged carbon dots (CDs-3) serve as a safe and highly efficient non-viral gene delivery vector.
- The CDs-3/siIhh system effectively regulates the Ihh signaling pathway and OA markers in chondrocytes.
- This novel CD-based vector holds significant potential for advancing osteoarthritis gene therapy due to its safety and efficacy.
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