Self-Assembled DNA-Protein Hybrid Nanospheres: Biocompatible Nano-Drug-Carriers for Targeted Cancer Therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Developing targeted drug delivery systems is crucial for effective cancer treatment.
• Hybrid nanostructures offer unique properties by combining biomolecules.
• DNA and protein-based nanostructures show potential due to biocompatibility and functionality.

Purpose of the Study:

• To develop and characterize novel hybrid nanospheres for targeted cancer therapy.
• To evaluate the drug-loading capacity, targeting ability, and in vivo imaging capabilities of these nanospheres.
• To assess the therapeutic efficacy and safety of the developed nanocarriers.

Main Methods:

• Fabrication of hybrid nanospheres via a one-pot, three-step self-assembly process involving DNA oligomers and streptavidin.
• Functionalization of nanospheres with MUC1-specific aptamers for targeted delivery and doxorubicin (Dox) loading via DNA intercalation.
• Characterization using agarose gel electrophoresis, dynamic light scattering (DLS), and transmission electron microscopy (TEM).
• In vitro evaluation of drug loading, release kinetics, specific cell binding (flow cytometry, confocal microscopy), and cytotoxicity.
• In vivo imaging and tumor targeting studies in a MUC1-positive 4T1 tumor-bearing mouse model.

Main Results:

• Successfully synthesized uniform, spherical DNA-streptavidin hybrid nanospheres.
• Demonstrated high doxorubicin loading capacity and sustained release characteristics.
• Confirmed MUC1-specific binding and enhanced cytotoxicity in MUC1-positive cancer cells via aptamer-mediated internalization.
• Achieved successful in vivo imaging and specific tumor targeting in a mouse model.
• Showed no significant systemic toxicity in normal mice.

Conclusions:

• Self-assembled DNA-streptavidin hybrid nanospheres are biocompatible and possess excellent drug-loading and targeting capabilities.
• Aptamer-functionalized nanospheres exhibit specific MUC1-cancer cell targeting and enhanced therapeutic efficacy.
• These hybrid nanospheres represent a promising platform for advanced nanomedical cancer therapies.
• The developed system allows for in vivo imaging and targeted drug delivery with minimal toxicity.