Tailored protein-conjugated DNA nanoplatform for synergistic cancer therapy

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapeutics

Background:

• Multidrug resistance (MDR) and targeted drug delivery are significant challenges in cancer treatment.
• Developing effective delivery systems is crucial for overcoming drug resistance and improving therapeutic outcomes.

Purpose of the Study:

• To design a multifunctional fusion protein-DNA conjugate for co-delivery of anticancer peptides and chemotherapeutic drugs.
• To create a nanocarrier capable of targeting both drug-resistant and drug-sensitive tumor cells.

Main Methods:

• A fusion protein was engineered, incorporating a PsTag polypeptide, a matrix metalloproteinase 2 (MMP2)-degradable domain, and a mitochondria-targeted pro-apoptotic peptide (KLAKLAKKLAKLAK).
• Doxorubicin was loaded into a DNA nanostructure pre-conjugated with the fusion protein, forming a dendrimer-like nanocarrier.
• The nanocarrier was designed for enhanced stability, tumor targeting, and controlled release.

Main Results:

• The developed nanocarrier selectively entered tumor cells.
• The system demonstrated synergistic antitumor activity.
• No significant adverse effects were observed, indicating good biocompatibility.

Conclusions:

• Protein-conjugated DNA nanocarriers represent a promising co-delivery system for synergistic cancer therapy.
• This approach offers a potential strategy to overcome multidrug resistance in cancer treatment.
• The nanocarrier system facilitates the combined delivery of protein/peptide and chemotherapeutic drugs.