A DNA-based nanocarrier for efficient cancer therapy.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Developing effective drug delivery systems for cancer therapy is crucial.
• Targeted delivery of chemotherapeutics like cisplatin can minimize systemic toxicity.
• Deoxyribonucleic acid nanostructures offer potential for controlled drug encapsulation and release.

Purpose of the Study:

• To create cisplatin-loaded deoxyribonucleic acid-nanothreads (CPT-DNA-NT) for enhanced targeted cytotoxicity.
• To investigate the cell internalization mechanism of CPT-DNA-NT mediated by scavenger receptors.
• To evaluate the in vitro efficacy and biocompatibility of CPT-DNA-NT in HeLa cells.

Main Methods:

• Fabrication of DNA-nanothreads (DNA-NT) using a circular-scaffold approach.
• Characterization of DNA-NT structure and uniformity using Atomic Force Microscopy (AFM).
• Assessment of DNA-NT integrity via native-polyacrylamide gel electrophoresis.
• Evaluation of cytotoxicity using MTT assay and flow cytometry.
• Confocal microscopy to visualize intracellular drug release and cell internalization.

Main Results:

• DNA-NTs exhibited uniform structure (50-150 nm diameter, 300-600 nm length) and confirmed integrity.
• Blank DNA-NT showed high biocompatibility with 92% cell viability at 512 nM.
• CPT-DNA-NT displayed superior cytotoxicity compared to free cisplatin due to sustained drug release.
• Targeted cell internalization and controlled intracellular release of cisplatin were observed.
• Flow cytometry indicated enhanced apoptosis (72.7%) with CPT-DNA-NT versus free cisplatin (64.4%).

Conclusions:

• CPT-DNA-NT effectively enhances targeted cytotoxicity and cell internalization in HeLa cells.
• Scavenger receptor-mediated endocytosis plays a key role in CPT-DNA-NT uptake.
• The developed nanothreads show promise as a biocompatible and effective drug delivery platform for cancer therapy.