Breakthrough in Cancer Gene Therapy: Zhejiang University Research

Researchers at Zhejiang University in Hangzhou, People's Republic of China, have made a significant contribution to the field of cancer gene therapy with the design of a multifunctional drug delivery system. This innovative system, employing a dendritic-DNA-based nanohydrogel, achieves precise release of therapeutic agents in response to the tumor microenvironment. The study's findings demonstrate enhanced cancer cell inhibition compared to single-agent treatments, highlighting the potential of this novel strategy for co-delivery of chemotherapy and gene silencing agents.

Key Takeaways:

• The research team designed a stimuli-responsive dendritic-DNA-based nanohydrogel as a nanocarrier for co-delivery of doxorubicin and HMGN5-mRNA-targeting antisense oligonucleotides.
• The nanocarrier, constructed from dendritic DNA with three crosslinking branches and one loading branch, enabled efficient incorporation of a shielding DNA/ASO complex and DOX encapsulation for chemotherapy.
• Cellular studies demonstrated significantly enhanced cancer cell inhibition compared to single-agent treatments, highlighting the combined effects of chemotherapy and gene silencing.
• The study provides a novel strategy for tumor-microenvironment-responsive co-delivery, enabling on-demand release of therapeutic agents to enhance combined chemo-gene therapy.
• The research was conducted at Zhejiang University, with financial support from the National Natural Science Foundation of China.
• Authors Jing Zhao, Jingyuan Wu, Yiqi Fan, Chao Yu, Le Yu, and Fangwei Shao contributed to the research.

Statistics:

• The study utilized a dendritic-DNA-based nanohydrogel as a nanocarrier for co-delivery of therapeutic agents.
• The nanocarrier enabled efficient incorporation of a shielding DNA/ASO complex, with a shielding efficiency of 70.5%.
• Cellular uptake studies demonstrated that the nanocarrier disassembled in the acidic tumor microenvironment, releasing DOX for chemotherapy and ASOs via toehold-mediated strand displacement (TMSD) for targeted gene silencing.
• The study demonstrated enhanced cancer cell inhibition with a cell viability of 15.6% compared to single-agent treatments.

Sources:

• A pH-Responsive Dendritic-DNA-Based Nanohydrogel for Dual Drug Delivery. Biomolecules, 2025,15(4):537. (Biomolecules - http://www.mdpi.com/journal/biomolecules)
• National Natural Science Foundation of China
• Zhejiang University Department of Chemistry, Hangzhou 310000, People's Republic of China